相关论文
2004 - Journal of the American Society of Nephrology : JASN
Clinical and molecular analysis of patients with renal hypouricemia in Japan-influence of URAT1 gene on urinary urate excretion.

Renal hypouricemia is an inherited and heterogeneous disorder characterized by increased urate clearance (CUA). The authors recently established that urate was reabsorbed via URAT1 on the tubular apical membrane and that mutations in SLC22A12 encoding URAT1 cause renal hypouricemia. This study was undertaken to elucidate and correlate clinical and genetic features of renal hypouricemia. The SLC22A12 gene was sequenced in 32 unrelated idiopathic renal hypouricemia patients, and the relationships of serum urate levels, and CUA/creatinine clearance (Ccr) to SLC22A12 genotype were examined. Uricosuric (probenecid and benzbromarone) and anti-uricosuric drug (pyrazinamide) loading tests were also performed in some patients. Three patients had exercise-induced acute renal failure (9.4%), and four patients had urolithiasis (12.5%). The authors identified eight new mutations and two previously reported mutations that result in loss of function. Thirty patients had SLC22A12 mutations; 24 homozygotes and compound heterozygotes, and 6 heterozygotes. Mutation G774A dominated SLC22A12 mutations (74.1% in 54 alleles). Serum urate levels were significantly lower and CUA/Ccr was significantly higher in heterozygotes compared with healthy subjects; these changes were even more significant in homozygotes and compound heterozygotes. These CUA/Ccr relations demonstrated a gene dosage effect that corresponds with the difference in serum urate levels. In contrast to healthy subjects, the CUA/Ccr of patients with homozygous and compound heterozygous SLC22A12 mutations was unaffected by pyrazinamide, benzbromarone, and probenecid. The findings indicate that SLC22A12 was responsible for most renal hypouricemia and that URAT1 is the primary reabsorptive urate transporter, targeted by pyrazinamide, benzbromarone, and probenecid in vivo.

2008 - Annals of surgery
A Randomized Clinical Trial on Sentinel Lymph Node Biopsy Versus Axillary Lymph Node Dissection in Breast Cancer: Results of the Sentinella/GIVOM Trial

Objective:The aim of this multicenter randomized trial was to assess the efficacy and safety of sentinel lymph node (SLN) biopsy compared with axillary lymph node dissection (ALND). Background:All studies on SLN biopsy in breast cancer report a variable false negative rate, whose prognostic consequences are still unclear. Methods:From May 1999 to December 2004, patients with breast cancer ≤3 cm were randomly assigned to receive SLN biopsy associated with ALND (ALND arm) or SLN biopsy followed by ALND only if the SLN was metastatic (SLN arm). The main aim was the comparison of disease-free survival in the 2 arms. Results:A total of 749 patients were randomized and 697 were available for analysis. SLNs were identified in 662 of 697 patients (95%) and positive SLNs were found in 189 of 662 patients (28.5%). In the ALND group, positive non-SLNs were found in 18 patients with negative SLN, giving a false negative rate of 16.7% (18 of 108). Postoperative side effects were significantly less in the SLN group and there was no negative impact of the SLN procedure on psychologic well being. At a median follow-up of 56 months, there were more locoregional recurrences in the SLN arm, and the 5-year disease-free survival was 89.9% in the ALND arm and 87.6% in the SLN arm, with a difference of 2.3% (95% confidence interval: −3.1% to 7.6%). However, the number of enrolled patients was not sufficient to draw definitive conclusions. Conclusion:SLN biopsy is an effective and well-tolerated procedure. However, its safety should be confirmed by the results of larger randomized trials and meta-analyses.

2011 - The American economic review
Selection on Moral Hazard in Health Insurance

We use employee-level panel data from a single firm to explore the possibility that individuals may select insurance coverage in part based on their anticipated behavioral ("moral hazard") response to insurance, a phenomenon we label "selection on moral hazard." Using a model of plan choice and medical utilization, we present evidence of heterogeneous moral hazard as well as selection on it, and explore some of its implications. For example, we show that, at least in our context, abstracting from selection on moral hazard could lead to over-estimates of the spending reduction associated with introducing a high-deductible health insurance option.

2005 - Hippocampus
Bilateral hippocampal volume reduction in adults with post‐traumatic stress disorder: A meta‐analysis of structural MRI studies

Over the last decade a significant number of studies have reported smaller hippocampal volume in individuals with symptoms of post‐traumatic stress disorder (PTSD) relative to control groups, and in some cases hemispheric asymmetries in this effect have been noted. However these reported asymmetries have not been in a consistent direction, and other well‐controlled studies have failed to observe any hippocampal volume difference. This paper reports a systematic review and meta‐analysis of studies in which hippocampal volume was estimated from magnetic resonance images in adult patients with PTSD. After applying a variety of selection criteria intended to minimize potential confounds in pooled effect‐size estimates, the meta‐analysis included 13 studies of adult patients with PTSD that compared the patients to well‐matched control groups, for a total of 215 patients and 325 control subjects. The studies varied with respect to participant age, gender distribution, source of trauma, severity of symptoms, duration of disorder, the nature of the control groups, and the methods employed for volumetric quantification. Despite these differences, pooled effect size calculations across the studies indicated significant volume differences in both hemispheres. On average PTSD patients had a 6.9% smaller left hippocampal volume and a 6.6% smaller right hippocampal volume compared with control subjects. These volume differences were smaller when comparing PTSD patients with control subjects exposed to similar levels of trauma, and larger when comparing PTSD patients to control subjects without significant trauma exposure. Such differences are consistent with the notion that exposure to stressful experiences can lead to hippocampal atrophy, although prospective studies would be necessary to unambiguously establish such a relationship. © 2005 Wiley‐Liss, Inc.

2013 - JAMA neurology
A multicenter study of glucocerebrosidase mutations in dementia with Lewy bodies.

IMPORTANCE While mutations in glucocerebrosidase (GBA1) are associated with an increased risk for Parkinson disease (PD), it is important to establish whether such mutations are also a common risk factor for other Lewy body disorders. OBJECTIVE To establish whether GBA1 mutations are a risk factor for dementia with Lewy bodies (DLB). DESIGN We compared genotype data on patients and controls from 11 centers. Data concerning demographics, age at onset, disease duration, and clinical and pathological features were collected when available. We conducted pooled analyses using logistic regression to investigate GBA1 mutation carrier status as predicting DLB or PD with dementia status, using common control subjects as a reference group. Random-effects meta-analyses were conducted to account for additional heterogeneity. SETTING Eleven centers from sites around the world performing genotyping. PARTICIPANTS Seven hundred twenty-one cases met diagnostic criteria for DLB and 151 had PD with dementia. We compared these cases with 1962 controls from the same centers matched for age, sex, and ethnicity. MAIN OUTCOME MEASURES Frequency of GBA1 mutations in cases and controls. RESULTS We found a significant association between GBA1 mutation carrier status and DLB, with an odds ratio of 8.28 (95% CI, 4.78-14.88). The odds ratio for PD with dementia was 6.48 (95% CI, 2.53-15.37). The mean age at diagnosis of DLB was earlier in GBA1 mutation carriers than in noncarriers (63.5 vs 68.9 years; P < .001), with higher disease severity scores. CONCLUSIONS AND RELEVANCE Mutations in GBA1 are a significant risk factor for DLB. GBA1 mutations likely play an even larger role in the genetic etiology of DLB than in PD, providing insight into the role of glucocerebrosidase in Lewy body disease.

2013 - BMJ
Fruit consumption and risk of type 2 diabetes: results from three prospective longitudinal cohort studies

Objective To determine whether individual fruits are differentially associated with risk of type 2 diabetes. Design Prospective longitudinal cohort study. Setting Health professionals in the United States. Participants 66 105 women from the Nurses’ Health Study (1984-2008), 85 104 women from the Nurses’ Health Study II (1991-2009), and 36 173 men from the Health Professionals Follow-up Study (1986-2008) who were free of major chronic diseases at baseline in these studies. Main outcome measure Incident cases of type 2 diabetes, identified through self report and confirmed by supplementary questionnaires. Results During 3 464 641 person years of follow-up, 12 198 participants developed type 2 diabetes. After adjustment for personal, lifestyle, and dietary risk factors of diabetes, the pooled hazard ratio of type 2 diabetes for every three servings/week of total whole fruit consumption was 0.98 (95% confidence interval 0.96 to 0.99). With mutual adjustment of individual fruits, the pooled hazard ratios of type 2 diabetes for every three servings/week were 0.74 (0.66 to 0.83) for blueberries, 0.88 (0.83 to 0.93) for grapes and raisins, 0.89 (0.79 to 1.01) for prunes, 0.93 (0.90 to 0.96) for apples and pears, 0.95 (0.91 to 0.98) for bananas, 0.95 (0.91 to 0.99) for grapefruit, 0.97 (0.92 to 1.02) for peaches, plums, and apricots, 0.99 (0.95 to 1.03) for oranges, 1.03 (0.96 to 1.10) for strawberries, and 1.10 (1.02 to 1.18) for cantaloupe. The pooled hazard ratio for the same increment in fruit juice consumption was 1.08 (1.05 to 1.11). The associations with risk of type 2 diabetes differed significantly among individual fruits (P<0.001 in all cohorts). Conclusion Our findings suggest the presence of heterogeneity in the associations between individual fruit consumption and risk of type 2 diabetes. Greater consumption of specific whole fruits, particularly blueberries, grapes, and apples, is significantly associated with a lower risk of type 2 diabetes, whereas greater consumption of fruit juice is associated with a higher risk.

1996 - International journal of radiation oncology, biology, physics
Radiotherapy with or without hyperthermia in the treatment of superficial localized breast cancer: results from five randomized controlled trials. International Collaborative Hyperthermia Group.

PURPOSE Claims for the value of hyperthermia as an adjunct to radiotherapy in the treatment of cancer have mostly been based on small Phase I or II trials. To test the benefit of this form of treatment, randomized Phase III trials were needed. METHODS AND MATERIALS Five randomized trials addressing this question were started between 1988 and 1991. In these trials, patients were eligible if they had advanced primary or recurrent breast cancer, and local radiotherapy was indicated in preference to surgery. In addition, heating of the lesions and treatment with a prescribed (re)irradiation schedule had to be feasible and informed consent was obtained. The primary endpoint of all trials was local complete response. Slow recruitment led to a decision to collaborate and combine the trial results in one analysis, and report them simultaneously in one publication. Interim analyses were carried out and the trials were closed to recruitment when a previously agreed statistically significant difference in complete response rate was observed in the two larger trials. RESULTS We report on pretreatment characteristics, the treatments received, the local response observed, duration of response, time to local failure, distant progression and survival, and treatment toxicity of the 306 patients randomized. The overall CR rate for RT alone was 41% and for the combined treatment arm was 59%, giving, after stratification by trial, an odds ratio of 2.3. Not all trials demonstrated an advantage for the combined treatment, although the 95% confidence intervals of the different trials all contain the pooled odds ratio. The greatest effect was observed in patients with recurrent lesions in previously irradiated areas, where further irradiation was limited to low doses. CONCLUSION The combined result of the five trials has demonstrated the efficacy of hyperthermia as an adjunct to radiotherapy for treatment of recurrent breast cancer. The implication of these encouraging results is that hyperthermia appears to have an important role in the clinical management of this disease, and there should be no doubt that further studies of the use of hyperthermia are warranted.

2007 - American journal of respiratory and critical care medicine
Continuous positive airway pressure treatment of mild to moderate obstructive sleep apnea reduces cardiovascular risk.

RATIONALE Obstructive sleep apnea (OSA) is linked to increased cardiovascular risk, but the impact of mild forms of OSA and their treatment on cardiovascular outcomes remains controversial. OBJECTIVES To prospectively investigate cardiovascular outcomes in treated versus untreated patients with OSA. METHODS Consecutive sleep laboratory patients with all degrees of OSA were included. Endpoints were nonfatal (myocardial infarction, stroke, and acute coronary syndrome requiring revascularization procedures) and fatal (death from myocardial infarction or stroke) cardiovascular events. MEASUREMENTS AND MAIN RESULTS Comparison of event-free survival rates in treated versus untreated patients (Kaplan-Meier estimates, log-rank test). Of 449 patients enrolled (age, 56.0 +/- 10.5 years; body mass index, 30.8 +/- 5.4 kg/m(2)), 364 patients received OSA treatment, and 85 patients remained untreated. Median follow-up was 72.0 months (range, 1-156). Mean apnea-hypopnea index before treatment was 30.9 +/- 21.8/hour in treated and 15.3 +/- 13.0/hour in untreated patients, but there were no differences in cardiovascular comorbidities or risk factors. In patients with mild-moderate OSA (n = 288), events were more frequent in untreated patients (estimated event-free survival at 10 yr, 51.8 vs. 80.3% [P < 0.001]; absolute risk reduction, 28.5%; number needed to treat to prevent one event/10 yr, 3.5). After adjustment for age, gender, cardiovascular risk factors, and comorbidities at baseline, OSA treatment was an independent predictor for events (hazard ratio, 0.36; 95% confidence interval, 0.21-0.62; P < 0.001). CONCLUSIONS OSA treatment was associated with a cardiovascular risk reduction of 64% independent from age and preexisting cardiovascular comorbidities. OSA treatment should be considered for primary and secondary cardiovascular prevention, even in milder OSA.

2000 - The New England journal of medicine
Safety of withholding heparin in pregnant women with a history of venous thromboembolism. Recurrence of Clot in This Pregnancy Study Group.

BACKGROUND Women with a history of venous thromboembolism may be at increased risk for venous thromboembolic events during pregnancy. In these women, the decision to give or withhold heparin in the antepartum period is controversial, because accurate estimates of the frequency of recurrent thromboembolic events if antepartum heparin is withheld are not available. METHODS We prospectively studied 125 pregnant women with a single previous episode of venous thromboembolism. Antepartum heparin was withheld, but anticoagulant therapy was given for four to six weeks post partum. Our primary objective was to determine the rate of antepartum recurrence of venous thromboembolism. Laboratory studies were performed to identify thrombophilia in 95 women. RESULTS Three of the 125 women (2.4 percent) had an antepartum recurrence of venous thromboembolism (95 percent confidence interval, 0.2 to 6.9 percent). There were no recurrences in the 44 women who had no evidence of thrombophilia and who also had a previous episode of thrombosis that was associated with a temporary risk factor. Among the 51 women with abnormal laboratory results or a previous episode of idiopathic thrombosis, or both, 3 (5.9 percent) had an antepartum recurrence of venous thromboembolism (95 percent confidence interval, 1.2 to 16.2 percent). CONCLUSIONS The risk of recurrent antepartum venous thromboembolism in women with a history of venous thromboembolism is low, and therefore routine antepartum prophylaxis with heparin is not warranted.

2005 - Chest
The relationship between reduced lung function and cardiovascular mortality: a population-based study and a systematic review of the literature.

STUDY OBJECTIVES Conditions that give rise to reduced lung function are frequently associated with low-grade systemic inflammation, which may lead to poor cardiovascular outcomes. We sought to determine the relationship between reduced FEV1 and cardiovascular mortality, independent of smoking. DESIGN Longitudinal population-based study and a meta-analysis of literature. SETTING Representative sample of the general population. PARTICIPANTS Participants of the first National Health and Nutrition Examination Survey Epidemiologic Follow-up Study who were 40 to 60 years of age at baseline assessment (n = 1,861). MEASUREMENTS AND RESULTS We compared the risk of cardiovascular mortality across quintiles of FEV1. Individuals in the lowest FEV1 quintile had the highest risk of cardiovascular mortality (relative risk [RR], 3.36; 95% confidence interval [CI], 1.54 to 7.34). Compared to FEV1 quintile 1, individuals in quintile 5 had a fivefold increase in the risk of death from ischemic heart disease (RR, 5.65; 95% CI, 2.26 to 14.13). We also performed a systematic review of large cohort studies (> 500 participants) that reported on the relationship between FEV1 and cardiovascular mortality (12 studies; n = 83,880 participants). Compared to participants in the highest FEV1 category, those with reduced FEV1 had a higher risk of cardiovascular mortality (pooled RR, 1.77; 95% CI, 1.56 to 1.97). CONCLUSIONS There is strong epidemiologic evidence to indicate that reduced FEV1 is a marker for cardiovascular mortality independent of age, gender, and smoking history.

2008 - Investigative radiology
Stability of Gadolinium-Based Magnetic Resonance Imaging Contrast Agents in Human Serum at 37°C

Objectives:Assessment of the complex stability and Gd3+ dissociation rate of all marketed gadolinium-based MRI contrast agents (GBCA) in human serum at pH 7.4 and 37°C. Methods and Results:The kinetic profiles of Gd3+ dissociation of GBCAs were determined by incubation for 15 days in human serum from healthy volunteers at a concentration of 1 mmol/L, pH 7.4, and 37°C. The initial rates of Gd3+ release and the amounts of Gd3+ released after 15 days were established by HPLC-ICP-MS analysis. In an attempt to simulate the situation in patients with end-stage renal disease who often have elevated serum phosphate levels, the influence of 10 mmol/L phosphate on Gd3+ dissociation was also investigated. The GBCAs were grouped and ranked in the following order according to their stabilities in native human serum at pH 7.4 and 37°C [% Gd3+ release after 15 days and initial rate (%/d) (95% confidence interval) in brackets]. Nonionic Linear GBCAs:Optimark [21 (19–22) %, 0.44 (0.40–0.51) %/d) and Omniscan [20 (17–20) %, 0.16 (0.15–0.17) %/d]. Ionic Linear GBCAs:Magnevist [1.9 (1.2–2.0) %, 0.16 (0.12–0.36) %/d], Multihance [1.9 (1.3–2.1) %, 0.18 (0.13–0.38) %/d], Vasovist [1.8 (1.4–1.9) %, 0.12 (0.11–0.18) %/d], and Primovist [1.1 (0.76–1.2) %, 0.07 (0.05–0.08) %/d]. Macrocyclic GBCAs:Gadovist, Prohance, and Dotarem (all < limit of quantification of 0.1%, <0.007%/d). In the presence of additional 10 mmol/L phosphate in serum, the initial Gd3+ release rates of the nonionic linear GBCAs, Omniscan, and Optimark increased about 100-fold, and, after 15 days, the amount of Gd3+ released from these agents was more than 75% higher than in native serum. The initial rates found for the ionic linear GBCAs increased about 12- to 30-fold, but, despite this, increase in the initial rate, the amount of Gd3+ released after 15 days was comparable to that in native serum. The elevated phosphate level did not lead to any measurable release of Gd3+ from the 3 macrocyclic GBCAs. Conclusions:The release of Gd3+ from all linear Gd complexes in human serum was several orders of magnitude greater than predicted by the conditional stability constants. After 15 days, release of Gd3+ from the nonionic linear GBCAs was about 10 times higher than from the ionic linear GBCAs. Elevated serum phosphate levels accelerated the release of Gd3+ from nonionic linear GBCAs and, to a lesser degree, from the ionic linear GBCAs. All 3 macrocyclic GBCAs remained stable in human serum at both normal and elevated phosphate levels.

2000 - Genetics
Codon-substitution models for heterogeneous selection pressure at amino acid sites.

Comparison of relative fixation rates of synonymous (silent) and nonsynonymous (amino acid-altering) mutations provides a means for understanding the mechanisms of molecular sequence evolution. The nonsynonymous/synonymous rate ratio (omega = d(N)d(S)) is an important indicator of selective pressure at the protein level, with omega = 1 meaning neutral mutations, omega < 1 purifying selection, and omega > 1 diversifying positive selection. Amino acid sites in a protein are expected to be under different selective pressures and have different underlying omega ratios. We develop models that account for heterogeneous omega ratios among amino acid sites and apply them to phylogenetic analyses of protein-coding DNA sequences. These models are useful for testing for adaptive molecular evolution and identifying amino acid sites under diversifying selection. Ten data sets of genes from nuclear, mitochondrial, and viral genomes are analyzed to estimate the distributions of omega among sites. In all data sets analyzed, the selective pressure indicated by the omega ratio is found to be highly heterogeneous among sites. Previously unsuspected Darwinian selection is detected in several genes in which the average omega ratio across sites is <1, but in which some sites are clearly under diversifying selection with omega > 1. Genes undergoing positive selection include the beta-globin gene from vertebrates, mitochondrial protein-coding genes from hominoids, the hemagglutinin (HA) gene from human influenza virus A, and HIV-1 env, vif, and pol genes. Tests for the presence of positively selected sites and their subsequent identification appear quite robust to the specific distributional form assumed for omega and can be achieved using any of several models we implement. However, we encountered difficulties in estimating the precise distribution of omega among sites from real data sets.

1992 - Archives of general psychiatry
A family study of obsessive-compulsive disorder.

BACKGROUND The causes of obsessive-compulsive disorder (OCD) are as yet unknown. Evidence of familial aggregation is one approach for investigating the role of genetics in the etiology of this condition. The current study was conducted to determine ifOCD is familial and to investigate possible familial subtypes. METHODS Eighty case probands were identified in 5 specialty OCD clinics and 73 community control probands were identified by random-digit dialing. These probands and their first-degree relatives (343 case and 300 control relatives) were blinded to group and evaluated by psychiatrists and doctoral-level clinical psychologists using semistructured instruments. Final diagnoses were assigned by a blinded-consensus procedure. The results were analyzed using logistic regression by the method of generalized estimating equations. RESULTS The lifetime prevalence of OCD was significantly higher in case compared with control relatives (11.7% vs 2.7%) (P<.001). Case relatives had higher rates of both obsessions and compulsions; however, this finding is more robust for obsessions. Age at onset of obsessive-compulsive symptoms in the case proband was strongly related to familiality (odds ratio, 0.92; confidence interval, 0.85-0.99) (P = .05); no case of OCD symptoms was detected in the relatives of probands whose age at onset of symptoms was 18 years or older. Probands with tics or obsessive-compulsive personality disorder were not more likely to have relatives with OCD than those without these features. CONCLUSIONS Obsessive-compulsive disorder is a familial disorder. Obsessions are more specific to the phenotype than are compulsions. Age at onset of OCD is valuable in characterizing a familial subtype.

2004 - Annals of surgery
Surgery Decreases Long-term Mortality, Morbidity, and Health Care Use in Morbidly Obese Patients

Objective:This study tested the hypothesis that weight-reduction (bariatric) surgery reduces long-term mortality in morbidly obese patients. Background:Obesity is a significant cause of morbidity and mortality. The impact of surgically induced, long-term weight loss on this mortality is unknown. Methods:We used an observational 2-cohort study. The treatment cohort (n = 1035) included patients having undergone bariatric surgery at the McGill University Health Centre between 1986 and 2002. The control group (n = 5746) included age- and gender-matched severely obese patients who had not undergone weight-reduction surgery identified from the Quebec provincial health insurance database. Subjects with medical conditions (other then morbid obesity) at cohort-inception into the study were excluded. The cohorts were followed for a maximum of 5 years from inception. Results:The cohorts were well matched for age, gender, and duration of follow-up. Bariatric surgery resulted in significant reduction in mean percent excess weight loss (67.1%, P < 0.001). Bariatric surgery patients had significant risk reductions for developing cardiovascular, cancer, endocrine, infectious, psychiatric, and mental disorders compared with controls, with the exception of hematologic (no difference) and digestive diseases (increased rates in the bariatric cohort). The mortality rate in the bariatric surgery cohort was 0.68% compared with 6.17% in controls (relative risk 0.11, 95% confidence interval 0.04–0.27), which translates to a reduction in the relative risk of death by 89%. Conclusions:This study shows that weight-loss surgery significantly decreases overall mortality as well as the development of new health-related conditions in morbidly obese patients.

2018 - Proceedings of the National Academy of Sciences
Global estimates of mortality associated with long-term exposure to outdoor fine particulate matter

Significance Exposure to outdoor concentrations of fine particulate matter is considered a leading global health concern, largely based on estimates of excess deaths using information integrating exposure and risk from several particle sources (outdoor and indoor air pollution and passive/active smoking). Such integration requires strong assumptions about equal toxicity per total inhaled dose. We relax these assumptions to build risk models examining exposure and risk information restricted to cohort studies of outdoor air pollution, now covering much of the global concentration range. Our estimates are severalfold larger than previous calculations, suggesting that outdoor particulate air pollution is an even more important population health risk factor than previously thought. Exposure to ambient fine particulate matter (PM2.5) is a major global health concern. Quantitative estimates of attributable mortality are based on disease-specific hazard ratio models that incorporate risk information from multiple PM2.5 sources (outdoor and indoor air pollution from use of solid fuels and secondhand and active smoking), requiring assumptions about equivalent exposure and toxicity. We relax these contentious assumptions by constructing a PM2.5-mortality hazard ratio function based only on cohort studies of outdoor air pollution that covers the global exposure range. We modeled the shape of the association between PM2.5 and nonaccidental mortality using data from 41 cohorts from 16 countries—the Global Exposure Mortality Model (GEMM). We then constructed GEMMs for five specific causes of death examined by the global burden of disease (GBD). The GEMM predicts 8.9 million [95% confidence interval (CI): 7.5–10.3] deaths in 2015, a figure 30% larger than that predicted by the sum of deaths among the five specific causes (6.9; 95% CI: 4.9–8.5) and 120% larger than the risk function used in the GBD (4.0; 95% CI: 3.3–4.8). Differences between the GEMM and GBD risk functions are larger for a 20% reduction in concentrations, with the GEMM predicting 220% higher excess deaths. These results suggest that PM2.5 exposure may be related to additional causes of death than the five considered by the GBD and that incorporation of risk information from other, nonoutdoor, particle sources leads to underestimation of disease burden, especially at higher concentrations.

1998 - The New England journal of medicine
Prepregnancy weight and the risk of adverse pregnancy outcomes.

BACKGROUND Obesity before pregnancy is associated with an increased risk of several adverse outcomes of pregnancy. The risk profiles among lean, normal, or mildly overweight women are not, however, well established. METHODS We studied the associations between prepregnancy body-mass index (defined as the weight in kilograms divided by the square of the height in meters) and the frequency of late fetal death, early neonatal death, preterm delivery, and delivery of a small-for-gestational-age infant in a population-based cohort of 167,750 women in Sweden in 1992 and 1993. The women were categorized as follows, according to body-mass index: lean, less than 20.0; normal, 20.0 through 24.9; overweight, 25.0 through 29.9; and obese, 30.0 or more. The estimates were adjusted for maternal age, parity, smoking, education, whether the mother was living with the father, and maternal height. RESULTS Among nulliparous women, the odds ratios for late fetal death were increased among women with higher body-mass-index values as compared with lean women, as follows: normal women, 2.2 (95 percent confidence interval, 1.2 to 4.1); overweight women, 3.2 (95 percent confidence interval, 1.6 to 6.2); and obese women, 4.3 (95 percent confidence interval, 2.0 to 9.3). Among parous women, only obese women had a significant increase in the risk of late fetal death (odds ratio, 2.0; 95 percent confidence interval, 1.2 to 3.3). Among nulliparous women, the risk of very preterm delivery (at < or =32 weeks' gestation) was significantly increased among obese as compared with lean women (odds ratio, 1.6; 95 percent confidence interval, 1.1 to 2.3), whereas among parous women, the risk was highest among those who were lean. The risk of delivering a small-for-gestational-age infant decreased more with increasing body-mass index among parous than among nulliparous women. CONCLUSIONS Higher maternal weight before pregnancy increases the risk of late fetal death, although it protects against the delivery of a small-for-gestational-age infant.

2019
Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes

Abstract Background The cardiovascular safety profile of dapagliflozin, a selective inhibitor of sodium–glucose cotransporter 2 that promotes glucosuria in patients with type 2 diabetes, is undefined. Methods We randomly assigned patients with type 2 diabetes who had or were at risk for atherosclerotic cardiovascular disease to receive either dapagliflozin or placebo. The primary safety outcome was a composite of major adverse cardiovascular events (MACE), defined as cardiovascular death, myocardial infarction, or ischemic stroke. The primary efficacy outcomes were MACE and a composite of cardiovascular death or hospitalization for heart failure. Secondary efficacy outcomes were a renal composite (≥40% decrease in estimated glomerular filtration rate to <60 ml per minute per 1.73 m2 of body-surface area, new end-stage renal disease, or death from renal or cardiovascular causes) and death from any cause. Results We evaluated 17,160 patients, including 10,186 without atherosclerotic cardiovascular disease, ...

2013 - Journal of internal medicine
Review of the key results from the Swedish Obese Subjects (SOS) trial – a prospective controlled intervention study of bariatric surgery

Obesity is a risk factor for diabetes, cardiovascular disease events, cancer and overall mortality. Weight loss may protect against these conditions, but robust evidence for this has been lacking. The Swedish Obese Subjects (SOS) study is the first long‐term, prospective, controlled trial to provide information on the effects of bariatric surgery on the incidence of these objective endpoints. The SOS study involved 2010 obese subjects who underwent bariatric surgery [gastric bypass (13%), banding (19%) and vertical banded gastroplasty (68%)] and 2037 contemporaneously matched obese control subjects receiving usual care. The age of participants was 37–60 years and body mass index (BMI) was ≥34 kg m−2 in men and ≥38 kg m−2 in women. Here, we review the key SOS study results published between 2004 and 2012. Follow‐up periods varied from 10 to 20 years in different reports. The mean changes in body weight after 2, 10, 15 and 20 years were −23%, −17%, −16% and −18% in the surgery group and 0%, 1%, −1% and −1% in the control group respectively. Compared with usual care, bariatric surgery was associated with a long‐term reduction in overall mortality (primary endpoint) [adjusted hazard ratio (HR) = 0.71, 95% confidence interval (CI) 0.54–0.92; P = 0.01] and decreased incidences of diabetes (adjusted HR=0.17; P < 0.001), myocardial infarction (adjusted HR = 0.71; P = 0.02), stroke (adjusted HR=0.66; P = 0.008) and cancer (women: adjusted HR = 0.58; P = 0.0008; men: n.s.]. The diabetes remission rate was increased severalfold at 2 years [adjusted odds ratio (OR) = 8.42; P < 0.001] and 10 years (adjusted OR = 3.45; P < 0.001). Whereas high insulin and/or high glucose at baseline predicted favourable treatment effects, high baseline BMI did not, indicating that current selection criteria for bariatric surgery need to be revised.

1987 - Arthritis and rheumatism
Mortality in systemic lupus erythematosus.

OBJECTIVE To examine mortality rates in the largest systemic lupus erythematosus (SLE) cohort ever assembled. METHODS Our sample was a multisite international SLE cohort (23 centers, 9,547 patients). Deaths were ascertained by vital statistics registry linkage. Standardized mortality ratio (SMR; ratio of deaths observed to deaths expected) estimates were calculated for all deaths and by cause. The effects of sex, age, SLE duration, race, and calendar-year periods were determined. RESULTS The overall SMR was 2.4 (95% confidence interval 2.3-2.5). Particularly high mortality was seen for circulatory disease, infections, renal disease, non-Hodgkin's lymphoma, and lung cancer. The highest SMR estimates were seen in patient groups characterized by female sex, younger age, SLE duration <1 year, or black/African American race. There was a dramatic decrease in total SMR estimates across calendar-year periods, which was demonstrable for specific causes including death due to infections and death due to renal disorders. However, the SMR due to circulatory diseases tended to increase slightly from the 1970s to the year 2001. CONCLUSION Our data from a very large multicenter international cohort emphasize what has been demonstrated previously in smaller samples. These results highlight the increased mortality rate in SLE patients compared with the general population, and they suggest particular risk associated with female sex, younger age, shorter SLE duration, and black/African American race. The risk for certain types of deaths, primarily related to lupus activity (such as renal disease), has decreased over time, while the risk for deaths due to circulatory disease does not appear to have diminished.

2007 - Journal of viral hepatitis
The impact of hepatitis C virus infection on survival in dialysis patients: meta‐analysis of observational studies

Summary.  The impact of hepatitis C virus (HCV) infection on mortality of patients receiving regular dialysis remains unclear. The assessment of the natural history of HCV in dialysis population is difficult because of the low progression of HCV‐related liver disease over time and the reduced life expectancy in patients with end‐stage renal disease. The aim of the study was to conduct a systematic review of the published medical literature concerning the impact of HCV infection on the survival of patients undergoing maintenance dialysis. The relative risk of mortality was regarded as the most reliable outcome end‐point. Study‐specific relative risks were weighted by the inverse of their variance to obtain fixed‐ and random‐effects pooled estimates for mortality with HCV across the published studies. We identified seven studies involving 11 589 unique patients on maintenance dialysis; two (29%) were case–control studies. Pooling of study results demonstrated that presence of anti‐HCV antibody was an independent and significant risk factor for death in patients on maintenance dialysis. The summary estimate for adjusted relative risk (aRR) (all‐cause mortality) was 1.34 with a 95% confidence interval (CI) of 1.13–1.59. Heterogeneity statistics, Ri = 0.48 (P‐value by Q‐test = 0.13). In a sensitivity analysis including only (n = 5) cohort studies, the pooled aRR was 1.38 (95% CI, 1.20–1.59); heterogeneity statistics Ri = 0.46. As a cause of death, hepatocellular carcinoma and liver cirrhosis were significantly more frequent among anti‐HCV‐positive than ‐negative dialysis patients. Our meta‐analysis indicates that anti‐HCV‐positive patients on dialysis have an increased risk of mortality compared with HCV‐negative patients. The excess risk of death in HCV‐positive patients may be at least partially attributed to chronic liver disease with its attendant complications.

World incidence of AKI: a meta-analysis.

I. Koulouridis
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B. Jaber
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D. Cruz
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J. Cerdá
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P. Susantitaphong
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Maher Abulfaraj
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Fahad Alqahtani
|
Ioannis Koulouridis
|
Maher M Abulfaraj

Abstract:BACKGROUND AND OBJECTIVES The burden of AKI around the globe has not been systematically examined. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A systematic review (2004-2012) of large cohort studies was conducted to estimate the world incidence of AKI and its stages of severity and associated mortality, and to describe geographic variations according to countries, regions, and their economies. AKI definitions were reclassified according to the Kidney Disease Improving Global Outcomes (KDIGO) staging system. Random-effects model meta-analyses and meta-regressions were used to generate summary estimates and explore sources of heterogeneity. RESULTS There were 312 studies identified (n=49,147,878) , primarily in hospital settings. Most studies originated from North America, Northern Europe, and Eastern Asia, from high-income countries, and from nations that spent ≥5% of the gross domestic product on total health expenditure. Among the 154 studies (n=3,585,911) that adopted a KDIGO-equivalent AKI definition, the pooled incidence rates of AKI were 21.6% in adults (95% confidence interval [95% CI], 19.3 to 24.1) and 33.7% in children (95% CI, 26.9 to 41.3). The pooled AKI-associated mortality rates were 23.9% in adults (95% CI, 22.1 to 25.7) and 13.8% in children (95% CI, 8.8 to 21.0). The AKI-associated mortality rate declined over time, and was inversely related to income of countries and percentage of gross domestic product spent on total health expenditure. CONCLUSIONS Using the KDIGO definition, 1 in 5 adults and 1 in 3 children worldwide experience AKI during a hospital episode of care. This analysis provides a platform to raise awareness of AKI with the public, government officials, and health care professionals.

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