Abalone peptide increases stress resilience and cost-free longevity via SKN-1-governed transcriptional metabolic reprogramming in C. elegans.

A major goal of healthy aging is to prevent declining resilience and increasing frailty, which are associated with many chronic diseases and deterioration of stress response. Here, we propose a loss-or-gain survival model, represented by the ratio of cumulative stress span to life span, to quantify stress resilience at organismal level. As a proof of concept, this is demonstrated by reduced survival resilience in Caenorhabditis elegans exposed to exogenous oxidative stress induced by paraquat or with endogenous proteotoxic stress caused by polyglutamine or amyloid-ß aggregation. Based on this, we reveal that a hidden peptide ("cryptide")-AbaPep#07 (SETYELRK)-derived from abalone hemocyanin not only enhances survival resilience against paraquat-induced oxidative stress but also rescues proteotoxicity-mediated behavioral deficits in C. elegans, indicating its capacity against stress and neurodegeneration. Interestingly, AbaPep#07 is also found to increase cost-free longevity and age-related physical fitness in nematodes. We then demonstrate that AbaPep#07 can promote nuclear localization of SKN-1/Nrf, but not DAF-16/FOXO, transcription factor. In contrast to its effects in wild-type nematodes, AbaPep#07 cannot increase oxidative stress survival and physical motility in loss-of-function skn-1 mutant, suggesting an SKN-1/Nrf-dependent fashion of these effects. Further investigation reveals that AbaPep#07 can induce transcriptional activation of immune defense, lipid metabolism, and metabolic detoxification pathways, including many SKN-1/Nrf target genes. Together, our findings demonstrate that AbaPep#07 is able to boost stress resilience and reduce behavioral frailty via SKN-1/Nrf-governed transcriptional reprogramming, and provide an insight into the health-promoting potential of antioxidant cryptides as geroprotectors in aging and associated conditions.

Exploring the clinical efficacy of a self-made acne prescription based on high-throughput sequencing.

BACKGROUND: We used high-throughput sequencing on skin microbial flora to assess the effectiveness of an acne prescription to formulate evidence for clinical decision-making. METHODS: We randomized 20 outpatients into two groups. The treatment group was given the acne formula orally. The control group took capsules of the Chinese patent medicine Qingre Anchuang. Both groups used a chloramphenicol tincture externally. After 14 days of treatment, we collected their skin samples and extracted the deoxyribonucleic acid for analysis. RESULTS: Forty samples were sequenced in this experiment, and of these, 1865 operational taxonomic units were obtained, belonging to 736 genera and 853 strains of 34 phyla. By alpha and beta diversity analysis, the abundance of microbial species in both the experimental and control groups before treatment was higher than after treatment, indicating the intervention drugs in this experiment had a bacteriostatic effect. Through the analysis of variance, we found that Subdoligranulum, Bifidobacterium, Bacteroides, and Akkermansia displayed large changes during the treatment. According to the linear discriminant analysis effect size, we discovered the bacteria groups with the greatest changes in the control group after treatment were Firmicutes, Clostridia, Proteobacteria, and Gammaproteobacteria. The flora of the experimental group before and after treatment were Corynebacteriaceae, Corynebacteriales, Cutibacterium, Propionibacteriales, Propionibacteriaceae, and Actinobacteria. CONCLUSION: The acne prescription had a reliable intervention effect on some epidermal microbial flora of patients with acne vulgaris and could inhibit the growth of acne-related microbial flora, such as Propionibacterium.

The impact of physician subspeciality on the quality of diabetes care for people living with HIV.

BACKGROUND: Management of comorbidities of people living with HIV (PLHIV) involves different care models, including providing diabetes care and HIV care by the same infectious diseases physician (IDP) ("consolidated care") or providing diabetes care by the physicians other than IDP ("shared care"). The impact of diabetes care model on PLHIV with diabetes mellitus (DM) has not been well-evaluated. METHODS: A nationwide cross-sectional sample in the Taiwan National Health Insurance Research Database was used to compare the performance rates of seven guideline-recommended tests provided by the different subspecialists. RESULTS: Of 523 PLHIV with DM, there were 54.88% (n = 287) in the consolidated care group and 45.12% (n = 236) in the shared care group. More patients in the consolidated care group received the tests of lipid profile (92.33% vs. 79.24%), creatinine (Cr) (93.73% vs. 78.39%), and alanine transaminase (ALT) (91.99% vs. 75.42%), but fewer received urine protein test (35.54% vs. 51.69%) and fundoscopic examination (8.01% vs. 33.90%). The two groups did not differ in the performance rates of serum fasting glucose and HbA1c. After controlling for demographic factors and diabetic severity, the consolidated group was less likely to miss the serum tests of lipid profile (odds ratio [OR]: 0.30), Cr (OR: 0.19), and ALT (OR: 0.23), but more often missed urine protein test (OR: 1.56) and fundoscopic examination (OR: 4.97). CONCLUSION: These findings suggest the need to focus on different process indicators of diabetes cares in different care models to enhance the diabetes care for PLHIV.

Antioxidant and antiaging effect of traditional Thai rejuvenation medicines in Caenorhabditis elegans.

OBJECTIVE: This study explored the rejuvenation mechanisms of Thai polyherbal medicines using different approaches, including in vitro methods, as well as a well-defined nematode model, Caenorhabditis elegans. METHODS: THP-R-SR012 decoction was selected from 23 polyherbal medicines, based on metal-chelating and chain-breaking antioxidant capacities. The influences of this extract on the survival and some stress biomarkers of C. elegans under paraquat-induced oxidative stress were evaluated. Furthermore, lifespan analysis and levels of lipofuscin accumulation were examined in senescent nematodes. The phytochemical profile of THP-R-SR012 was analyzed. RESULTS: Supplementation with THP-R-SR012 decoction significantly increased the mean lifespan and reduced the oxidative damage to C. elegans under oxidative stress conditions. Further, THP-R-SR012 supplementation slightly influenced the lifespan and the level of lipofuscin accumulation during adulthood. Antioxidant-related phytochemical constituents of THP-R-SR012 decoction were rutin, naringenin, 3,4-dihydroxybenzoic acid, gallic acid, glycyrrhizic acid, demethoxycurcumin and 18α-glycyrrhetinic acid. CONCLUSION: The antioxidant potential of THP-R-SR012 was due to its scavenging properties, its enhancement of antioxidant-related enzyme activities, and the presence of the antioxidant-related compound. These results support the traditional use of THP-R-SR012 decoction as a tonic for nourishing and strengthening the whole body.

Insulin and Metformin Control Cell Proliferation by Regulating TDG-Mediated DNA Demethylation in Liver and Breast Cancer Cells.

Type 2 diabetes mellitus (T2DM) is a frequent comorbidity of cancer. Hyperinsulinemia secondary to T2DM promotes cancer progression, whereas antidiabetic agents, such as metformin, have anticancer effects. However, the detailed mechanism for insulin and metformin-regulated cancer cell proliferation remains unclear. This study identified a mechanism by which insulin upregulated the expression of c-Myc, sterol regulatory element-binding protein 1 (SREBP1), and acetyl-coenzyme A (CoA) carboxylase 1 (ACC1), which are important regulators of lipogenesis and cell proliferation. Thymine DNA glycosylase (TDG), a DNA demethylase, was transactivated by c-Myc upon insulin treatment, thereby decreasing 5-carboxylcytosine (5caC) abundance in the SREBP1 promoter. On the other hand, metformin-activated AMP-activated protein kinase (AMPK) increased DNA methyltransferase 3A (DNMT3A) activity to increase 5-methylcytosine (5mC) abundance in the TDG promoter. This resulted in decreased TDG expression and enhanced 5caC abundance in the SREBP1 promoter. These findings demonstrate that c-Myc activates, whereas AMPK inhibits, TDG-mediated DNA demethylation of the SREBP1 promoter in insulin-promoted and metformin-suppressed cancer progression, respectively. This study indicates that TDG is an epigenetic-based therapeutic target for cancers associated with T2DM.

Physician code creep after the initiation of outpatient volume control program and implications for appropriate ICD-10-CM coding.

BACKGROUND: Most studies on the physician code creep (i.e., changes in case mix record-keeping practices to improve reimbursement) have focused on episodes (inpatient hospitalizations or outpatient procedures). Little is known regarding changes in diagnostic coding practices for better reimbursement among a fixed cohort of patients with chronic diseases. METHODS: To examine whether physicians in tertiary medical centers changed their coding practices after the initiation of the Outpatient Volume Control Program (OVCP) in Taiwan, we conducted a retrospective observational study of four patient cohorts (two interventions and two controls) from January 2016 to September 2017 in Taiwan. The main outcomes were the number of outpatient visits with four coding practices: 1) OVCP monitoring code recorded as primary diagnosis; 2) OVCP monitoring code recorded as secondary diagnosis; 3) non-OVCP monitoring code recorded as primary diagnosis; 4) non-OVCP monitoring code recorded as secondary diagnosis. RESULTS: The percentage change of the number of visits with coding practice 1 between 2016Q1 and 2017Q3 was - 74% for patients with hypertension and - 73% with diabetes in tertiary medical centers and - 23% and - 17% in clinics, respectively. By contrast, the percentage changes of coding practice 3 were + 73% for patients with hypertension and + 46% for patients with diabetes in tertiary medical centers and - 19% and - 2% in clinics, respectively. CONCLUSIONS: Physician code creep occurred after the initiation of the OVCP. Education regarding appropriate outpatient coding for physicians will be relatively effective when proper coding is related to reimbursement.

The moderator effect of retention in care on late presentation in HIV-infected patients.

The moderator effect of retention in care on late presenters in HIV patients has not been well evaluated. A nationwide cohort study focusing on HIV-infected patients with new engagement in care was conducted by using the Taiwan National Health Insurance Research Database. Retention in care was defined based on the healthcare utilization in the first year after engaging in HIV care. Then, the impact of late presentation, retention in care, and their interaction on the risk of subsequent hospitalizations due to opportunistic infections (OIs-hospitalizations) in the second year were examined. More than half (59.38%) of the total patients (n = 9112) were retained in care in the first year, 8.63% were late presenters, and 110 (1.21%) patients had subsequent hospitalization in the second year. Late presentation and non-retention were independent predictors of OIs-hospitalizations in the second year (OR: 2.58 and OR: 3.27, respectively) and the interaction between them was statistically significant (non-retention in care × late presentation, OR: 3.82). This study showed that retention in care in the first year is a moderator providing a stronger protective effect for late presenters than early presenters. Our findings call for policymakers to develop different strategies for early or late presenters.

Changes in drowning mortality rates and quality of reporting from 2004-2005 to 2014-2015: a comparative study of 61 countries.

BACKGROUND: This study assessed international variations in changes in drowning mortality rates and the quality of reporting specific information in death certificates over the past decade. METHODS: Drowning mortality data of 61 countries were extracted from the World Health Organization Mortality Database. We calculated the percentage change (PC) in age-standardized drowning mortality rates and percentage of drowning deaths reported with unspecified codes between 2004 and 2005 and 2014-2015. RESULTS: Of the 61 countries studied, 50 exhibited a reduction in drowning mortality rates from 2004 to 2005 to 2014-2015. Additionally, five countries-Lithuania, Moldova, Kyrgyzstan, Romania, and El Salvador-with a high mortality rate in 2004-2005 (> 40 deaths per 100,000) showed improvement (PC < - 32%). By contrast, four countries-South Africa, Guyana, Morocco, and Guatemala-exhibited a more than twofold increase in mortality rates. Regarding the quality of reporting, 34 countries exhibited a decrease in the percentage of unspecified codes. Additionally, three countries-Paraguay, Serbia, and Croatia-with moderate and high percentages of unspecified codes (> 40%) exhibited a marked reduction (PC < - 60%), whereas three countries-Malaysia, Belgium, and Nicaragua-exhibited a notable increase. CONCLUSIONS: Large international variations in the extent of changes in drowning mortality rates and the quality of reporting specific information on the death certificate were observed during the study period.

Health care utilization pattern prior to maltreatment among children under five years of age in Taiwan.

BACKGROUND: Several studies have hypothesized that the pattern of health care utilization among maltreated children differ from others without the experience. However, the conclusions have not been consistent. OBJECTIVE: The study aims to examine whether the pattern of health care utilization among children 0-5 years old with maltreatment different from their counterparts without maltreatment in Taiwan. SUBJECTS AND SETTING: All children born in 2007 in Taiwan. METHOD: This is a population-based and case-controlled study. Cases are children under five years of ago with maltreatment-related diagnosis in the claims data of the National Health Insurance in Taiwan during the 2007-2013 period. For each case, there were 10 birth date-matched controls. Exposure variables include the number of injury or non-injury-related outpatients, emergency department (ED) visits, and hospitalization. Multivariate models were employed, with adjustment for sex, urbanization level, and comorbidities of children. RESULTS: Of children born in 2007, 382 had maltreatment-related diagnosis during the age of 0-5. The adjusted odds ratio (aOR) for having two or more ED visits with or without injury-related diagnosis is 3.52 (95% CI 1.75-7.07) and 2.0-0 (95% CI 1.47-2.72), respectively. Children with maltreatment also had significantly higher number of hospitalization without injury-related diagnosis and aOR for those having two more hospitalizations stands at 2.47 (95% CI 1.59-3.83). CONCLUSIONS: Children with maltreatment when 0-5 years old had higher number of ED visits with injury-related diagnosis, as well as hospitalization without injury-related diagnosis. Recognition of the health care utilization is conducive to early identification of children with risk for maltreatment.

Changes in the number and causes of maternal deaths after the introduction of pregnancy checkbox on the death certificate in Taiwan.

OBJECTIVE: To examine changes in the number and causes of maternal deaths after the introduction of pregnancy checkbox on the death certificate in January 2014 in Taiwan. MATERIALS AND METHODS: We first used the cause-of-death (COD) mortality data for years 2010 through 2017 to examine the number of deaths by item of pregnancy checkbox. We then compared the distribution of the causes of maternal deaths before and after the introduction of pregnancy checkbox. RESULTS: Between 2014 and 2017, 111 women died, for whom the certifiers indicated the following in the pregnancy checkbox items: 2 (pregnant at the time of death; n = 10), 3 (died within 42 days after the termination of pregnancy; n = 64), and 4 (died between 43 days and 1 year after the termination of pregnancy; n = 37). However, in only 61 of the 111 deaths, the certifiers reported pregnancy or delivery-related diagnosis in the COD section of the death certificate-5 each for items 2 and 4 and 51 for item 3. The number of maternal deaths was 55 in 2010-2013; this number increased to 82 in 2014-2017. A decline in the percentage of maternal deaths from obstetric hemorrhage was noted from 38% (21/55) in 2010-2013 to 21% (17/82) in 2014-2017. CONCLUSION: The number of maternal deaths increased, and the distribution of causes of maternal deaths changed after the introduction of pregnancy checkbox. Additional studies are required to examine the possible misclassification of pregnancy-associated deaths indicated in the pregnancy checkbox.

Comparing regional neonatal mortality rates: the influence of registration of births as live born for birth weight <500 g in Taiwan.

OBJECTIVE: To investigate regional variation in the registration of births (still+live) as live born for birth weight <500 g and the impact on the city/county ranking of neonatal mortality rate (NMR) in Taiwan. DESIGN: Population-based cross-sectional ecological study. SETTING: 20 cities/counties in Taiwan. PARTICIPANTS: Registered births for birth weight <500 g and neonatal deaths in 2015-2016. MAIN OUTCOME MEASURES: City/county percentage of births <500 g registered as live born and ranking of city/county NMR (deaths per 1000 live births) including and excluding live births <500 g. RESULTS: The percentage of births <500 g registered as live born ranged from 0% in Keelung City (0/26) and Penghu County (0/4) to 20% in Taipei City (112/558), 24% in Hsinchu County (5/21) and 28% in Hualien County (9/32). The change in city/county ranking of NMR from including to excluding live births <500 g was most prominent in Taipei City (from the 15th to the 1st) followed by Kaohsiung City (from the 18th to the 14th). CONCLUSIONS: The city/county NMR in Taiwan is influenced by variation in the registration of live born for births with uncertain viability. We recommend presenting city/county NMR using both criteria (with or without minimum threshold of gestation period or birth weight) for better interpretation of the findings of comparisons of city/county NMR.

Inhibition of Abeta Proteotoxicity by Paeoniflorin in Caenorhabditis elegans Through Regulation of Oxidative and Heat Shock Stress Responses.

Alzheimer's disease (AD) is a common form of dementia and amyloid-ß peptide (Aß) aggregation is considered to be one of its main causes. Paeoniflorin has been previously shown to attenuate cognitive damage inflicted by exogenous Aß protein. Using transgenic Caenorhabditis elegans models expressing human Aß1-42, we demonstrate here that paeoniflorin can delay progressive paralysis caused by endogenous Aß expression and reduce the amount of toxic Aß oligomers in vivo, although it has no effect on Aß aggregation in vitro. Paeoniflorin does not, however, affect the lifespan of either wild-type or AD-like nematodes, implying a mechanism independent of a general antiaging effect. We then demonstrate that paeoniflorin can reduce reactive oxygen species levels in C. elegans AD models, which may contribute to its in vivo suppression of Aß toxicity. Moreover, paeoniflorin is shown to upregulate the expression of the small heat shock protein HSP-16.2 as it is capable of increasing the hsp-16.2 transcript level in wild-type as well as AD-like nematodes and enhancing the fluorescence intensity in hsp-16.2::GFP nematodes. Taken together, our findings demonstrate the underlying mechanisms of the protective effect of paeoniflorin against age-onset Aß proteotoxicity, which are, in part, connected with oxidative and heat shock stress responses.

A meta-analysis of the impact of human leukocyte antigen-G on the outcomes of IVF/ICSI.

This analysis was performed to determine whether the presence of soluble human leukocyte antigen-G (sHLA-G) in embryo culture medium is predictive of clinical outcomes in IVF treatment. The outcomes of implantation, clinical pregnancy, multiple pregnancy and miscarriage, between groups with and without sHLA-G in embryo culture media, were analysed. Fifteen studies with a total of 6170 cases were included. Ten of them were prospective studies while five were retrospective studies. Embryo culture media with sHLA-G were associated with significantly higher implantation rate and clinical pregnancy rate when compared with those without; the odd ratios (ORs) were 2.66 [95% confidence interval (CI): 1.75-4.06, P < 0.00001], 3.79 (95% CI: 2.69-5.33, P < 0.00001), respectively. There was no significant difference in the rate of multiple pregnancy (OR: 1.87, 95% CI: 0.55-6.31) and miscarriage (OR: 0.77, 95% CI: 0.52-1.16). The results suggested that the presence of sHLA-G in the embryo culture medium favoured higher implantation rate and pregnancy rate. However, the conclusion needs to be consolidated by further clinical studies using a more precise method of determination of sHLA-G and research on the physiological and molecular mechanisms of the beneficial effect of sHLA-G on early embryo development and implantation.

Prevalence of hand syndromes among patients with diabetes mellitus in Taiwan: A population-based study.

BACKGROUND: Population-based data for diabetic hand syndrome (DHS) are limited. The aim of the present epidemiological study was to estimate the overall and cause-specific prevalence and rate ratio (RR) of DHS in patients with diabetes. METHODS: The present study was a cross-sectional study based on a random sample of 57 093 diabetics and matched controls, both identified from Taiwan National Health Insurance claims in 2010. The DHS analyzed in the present study included carpal tunnel syndrome (CTS), stenosing flexor tenosynovitis (SFT), limited joint mobility (LJM), and Dupuytren's disease (DD). RESULTS: The prevalence of overall DHS was estimated at 2472 per 105 for the diabetics, compared with 1641 per 105 for the controls, representing a prevalence RR of 1.51 (95 % confidence interval [CI] 1.39-1.64). Stratified analyses further revealed that the significantly increased prevalence of overall DHS was more evident in females than males (1.59 vs 1.36) and was only noted in diabetics aged ≥35 years. Cause-specific analysis suggested that patients with diabetes had the highest prevalence of CTS (1244 per 105 ), followed by SFT (1209 per 105 ), LJM (39 per 105 ), and DD (6 per 105 ). In addition, diabetes was only significantly associated with CTS (RR 1.34; 95 % CI 1.20-1.51) and SFT (1.74; 95 % CI 1.54-1.97). CONCLUSION: The prevalence of overall and certain cause-specific DHS was significantly elevated in patients with diabetes in Taiwan.

Medical claims-based case-control study of temporal relationship between clinical visits for hand syndromes and subsequent diabetes diagnosis: implications for identifying patients with undiagnosed type 2 diabetes mellitus.

OBJECTIVES: To investigate whether a temporal relationship is present between clinical visits for diabetes-related hand syndromes (DHSs) and subsequent type 2 diabetes mellitus (T2DM) diagnosis and, accordingly, whether DHSs can be used for identifying patients with undiagnosed T2DM. DESIGN: This study had a case-control design nested within a cohort of 1 million people from the general population, which was followed from 2005 to 2010. The odds of prior clinical visits for DHSs, namely carpal tunnel syndrome (CTS), flexor tenosynovitis, limited joint mobility and Dupuytren's disease, were estimated for cases and controls. We used a conditional logistic regression model to estimate the OR and 95% CI of T2DM in association with a history of DHSs. The validity and predictive value of using the history of DHSs in predicting T2DM diagnosis were calculated. SETTING: Taiwan National Health Insurance medical claims. PARTICIPANTS: We identified 33 571 patients receiving a new diagnosis of T2DM (cases) between 2005 and 2010. Each T2DM case was matched with 5 controls who had the same sex and birth year and were alive on the date of T2DM diagnosis. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was T2DM diagnosis. RESULTS: The OR of T2DM in association with prior clinical visits was significantly increased for overall DHS and CTS, being 1.15 (95% CI 1.10 to 1.20) and 1.22 (95% CI 1.16 to 1.29), respectively. Moreover, 11% of patients with T2DM made clinical visits for CTS within 3 months prior to T2DM diagnosis. The history of DHSs had low sensitivity (<0.1% to 5.2%) and a positive predictive value (9.9% to 11.7%) in predicting T2DM. CONCLUSIONS: Despite the unsatisfactory validity and performance of DHSs as a clinical tool for detecting patients with undiagnosed T2DM, this study provided evidence that clinical visits for DHSs, particularly for CTS, can be a sign of undiagnosed T2DM.

Risk of Hand Syndromes in Patients With Diabetes Mellitus: A Population-Based Cohort Study in Taiwan.

The aim of this study was to assess the overall and cause-specific incidences of diabetic hand syndromes (DHS) in patients with diabetes mellitus (DM) by using age and sex stratifications.The DM and control cohorts comprised 606,152 patients with DM and 609,970 age- and sex-matched subjects, respectively, who were followed up from 2000 to 2008. We estimated the incidence densities (IDs) of overall and cause-specific DHS, namely carpal tunnel syndrome (CTS), stenosing flexor tenosynovitis (SFT), limited joint mobility (LJM), and Dupuytren disease (DD), and calculated the hazard ratios (HRs) of DHS in relation to DM by using a Cox proportional hazards model with adjustment for potential confounders.Over a 9-year period, 51,207 patients with DM (8.45%) and 39,153 matched controls (6.42%) sought ambulatory care visits for various DHS, with an ID of 117.7 and 80.7 per 10,000 person-years, respectively. The highest cause-specific ID was observed for CTS, followed by SFT, LJM, and DD, regardless of the diabetic status. After adjustment for potential confounders, patients with DM had a significantly high HR of overall DHS (1.51, 95% confidence interval [CI] = 1.48-1.53). Men and women aged <35 years had the highest HR (2.64, 95% CI = 2.15-3.24 and 2.99, 95% CI = 2.55-3.50, respectively). Cause-specific analyses revealed that DM was more strongly associated with SFT (HR = 1.90, 95% CI = 1.86-1.95) and DD (HR = 1.83, 95% CI = 1.39-2.39) than with CTS (HR = 1.31, 95% CI = 1.28-1.34) and LJM (HR = 1.24, 95% CI = 1.13-1.35).Men and younger patients with DM have the highest risk of DHS. Certain hand syndromes, such as SFT and DD, were more strongly associated with DM than with other syndromes and require the attention of clinicians.

Using cluster analysis to identify phenotypes and validation of mortality in men with COPD.

PURPOSE: Cluster analysis has been proposed to examine phenotypic heterogeneity in chronic obstructive pulmonary disease (COPD). The aim of this study was to use cluster analysis to define COPD phenotypes and validate them by assessing their relationship with mortality. METHODS: Male subjects with COPD were recruited to identify and validate COPD phenotypes. Seven variables were assessed for their relevance to COPD, age, FEV(1) % predicted, BMI, history of severe exacerbations, mMRC, SpO(2), and Charlson index. COPD groups were identified by cluster analysis and validated prospectively against mortality during a 4-year follow-up. RESULTS: Analysis of 332 COPD subjects identified five clusters from cluster A to cluster E. Assessment of the predictive validity of these clusters of COPD showed that cluster E patients had higher all cause mortality (HR 18.3, p < 0.0001), and respiratory cause mortality (HR 21.5, p < 0.0001) than those in the other four groups. Cluster E patients also had higher all cause mortality (HR 14.3, p = 0.0002) and respiratory cause mortality (HR 10.1, p = 0.0013) than patients in cluster D alone. CONCLUSION: COPD patient with severe airflow limitation, many symptoms, and a history of frequent severe exacerbations was a novel and distinct clinical phenotype predicting mortality in men with COPD.

An easy-to-implement approach for analyzing case-control and case-only studies assuming gene-environment independence and Hardy-Weinberg equilibrium.

The case-control study is a simple and an useful method to characterize the effect of a gene, the effect of an exposure, as well as the interaction between the two. The control-free case-only study is yet an even simpler design, if interest is centered on gene-environment interaction only. It requires the sometimes plausible assumption that the gene under study is independent of exposures among the non-diseased in the study populations. The Hardy-Weinberg equilibrium is also sometimes reasonable to assume. This paper presents an easy-to-implement approach for analyzing case-control and case-only studies under the above dual assumptions. The proposed approach, the 'conditional logistic regression with counterfactuals', offers the flexibility for complex modeling yet remains well within the reach to the practicing epidemiologists. When the dual assumptions are met, the conditional logistic regression with counterfactuals is unbiased and has the correct type I error rates. It also results in smaller variances and achieves higher powers as compared with using the conventional analysis (unconditional logistic regression).

Reducing population stratification bias: stratum matching is better than exposure.

OBJECTIVE: Genetic studies of complex human diseases rely heavily on the epidemiologic association paradigm, particularly the population-based case-control designs. This study aims to compare the matching effectiveness in terms of bias reduction between exposure matching and stratum matching. STUDY DESIGN AND SETTING: Formulas for population stratification bias were derived. An index of matching effectiveness was constructed to compare the two types of matching. RESULTS: It was found that exposure matching can paradoxically increase the magnitude of population stratification bias sometimes, whereas stratum matching can guarantee to reduce it. CONCLUSION: The authors propose two simple rules for genetic association studies: (a) to match on anything that helps to delineate population strata such as race, ethnicity, nationality, ancestry, and birthplace and (b) to match on an exposure only when it is a strong predictor of the disease and is expected to have great variation in prevalence across population strata.