Alcohol and risk of non-traumatic bleeding events requiring hospital care in the general population: A prospective cohort study

Abstract STUDY QUESTION Do sperm mitochondrial DNA measures predict probability of pregnancy among couples in the general population? SUMMARY ANSWER Those with high sperm mitochondrial DNA copy number (mtDNAcn) had as much as 50% lower odds of cycle-specific pregnancy, and 18% lower probability of pregnancy within 12 months. WHAT IS KNOWN ALREADY Semen parameters have been found to poorly predict reproductive success yet are the most prevalent diagnostic tool for male infertility. Increased sperm mtDNAcn and mitochondrial DNA deletions (mtDNAdel) have been associated with decreased semen quality and lower odds of fertilization in men seeking fertility treatment. STUDY DESIGN, SIZE, DURATION A population-based prospective cohort study of couples discontinuing contraception to become pregnant recruited from 16 US counties from 2005 to 2009 followed for up to 16 months. PARTICIPANTS/MATERIALS, SETTING, METHODS Sperm mtDNAcn and mtDNAdel from 384 semen samples were assessed via triplex probe-based quantitative PCR. Probability of pregnancy within 1 year was compared by mitochondrial DNA, and discrete-time proportional hazards models were used to evaluate the relations with time-to-pregnancy (TTP) with adjustment for covariates. MAIN RESULTS AND THE ROLE OF CHANCE Higher sperm mtDNAcn was associated with lower pregnancy probability within 12 months and longer TTP. In unadjusted comparisons by quartile (Q), those in Q4 had a pregnancy probability of 63.5% (95% CI: 53.1% to 73.1%) compared to 82.3% (95% CI: 73.2% to 89.9%) for Q1 (P = 0.002). Similar results were observed in survival analyses adjusting for covariates to estimate fecundability odds ratios (FORs) comparing mtDNAcn in quartiles. Relative to those in Q1 of mtDNAcn, FORs (95% CI) were for Q2 of 0.78 (0.52 to 1.16), Q3 of 0.65 (0.44 to 0.96) and Q4 of 0.55 (0.37 to 0.81), and this trend of decreasing fecundability with increasing mtDNAcn quartile was statistically significant (FOR per log mtDNAcn = 0.37; P < 0.001). Sperm mtDNAdel was not associated with TTP. LIMITATIONS, REASONS FOR CAUTION This prospective cohort study consisted primarily of Caucasian men and women and thus large diverse cohorts are necessary to confirm the associations between sperm mtDNAcn and couple pregnancy success in other races/ethnicities. WIDER IMPLICATIONS OF THE FINDINGS Our results demonstrate that sperm mtDNAcn has utility as a biomarker of male reproductive health and probability of pregnancy success in the general population. STUDY FUNDING/COMPETING INTEREST(S) This work was funded in part by the National Institute of Environmental Health Sciences, National Institutes of Health (R01-ES028298; PI: J.R.P.) and the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (Contracts N01-HD-3-3355, N01-HD-3-3356 and N01-HD-3-3358). The authors declare no competing interests. TRIAL REGISTRATION NUMBER N/A

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Mediterranean diet and mortality in the elderly: a prospective cohort study and a meta-analysis

British Journal Of Nutrition ◽

10.1017/s0007114518002179 ◽

2018 ◽

Vol 120 (8) ◽

pp. 841-854 ◽

Cited By ~ 28

Author(s):

Marialaura Bonaccio ◽

Augusto Di Castelnuovo ◽

Simona Costanzo ◽

Alessandro Gialluisi ◽

Mariarosaria Persichillo ◽

...

Keyword(s):

Cohort Study ◽

General Population ◽

Mediterranean Diet ◽

Prospective Cohort Study ◽

Prospective Studies ◽

Prospective Cohort ◽

Lower Risk ◽

Meta Analysis ◽

The Elderly ◽

Prolonged Survival

AbstractThe Mediterranean diet (MD) has been associated with prolonged survival in the general population, but no meta-analysis has apparently investigated the potential health benefits in relation to mortality in the elderly. We performed a longitudinal analysis on 5200 individuals aged ≥65 years identified within the general population recruited in the Moli-sani study cohort (2005–2010). Adherence to the MD was appraised by the a priori Mediterranean diet score (MDS; range 0–9). Survival estimates were derived using Cox regression and competing risk models. For the meta-analysis, PubMed and Scopus databases were searched from inception until April 2018 to identify prospective studies on the MD and death risk in the elderly. Over a median follow-up of 8·1 years, a total of 900 deaths were ascertained in the elderly sub-sample of the Moli-sani cohort. A one-point increase in the MDS was associated with lower risk of all-cause, coronary artery disease/cerebrovascular and non-cardiovascular/non-cancer mortality (multi-variable hazard ratio (HR)=0·94; 95 % CI 0·90, 0·98; HR=0·91; 95 % CI 0·83, 0·99 and HR=0·89; 95 % CI 0·81, 0·96, respectively). In a meta-analysis of seven prospective studies, including our results, for a total of 11 738 participants and 3874 deaths, one-point increment in MDS was associated with 5 % (4–7 %) lower risk of all-cause death. An inverse linear dose–response relationship was found from a meta-analysis including three studies. In conclusion, a prospective cohort study and a meta-analysis showed that closer adherence to the MD was associated with prolonged survival in elderly individuals, suggesting the appropriateness for older persons to adopt/preserve the MD to maximise their prospects for survival.

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Spontaneous abortion: A prospective cohort study of younger women from the general population in Denmark. Validation, occurrence and risk determinants

Acta Obstetricia Et Gynecologica Scandinavica ◽

10.1080/00016340500494887 ◽

2006 ◽

Vol 85 (4) ◽

pp. 467-475 ◽

Cited By ~ 55

Author(s):

L. Buss ◽

J. Tolstrup ◽

C. Munk ◽

T. Bergholt ◽

B. Ottesen ◽

...

Keyword(s):

Cohort Study ◽

General Population ◽

Spontaneous Abortion ◽

Prospective Cohort Study ◽

Prospective Cohort ◽

Younger Women ◽

Risk Determinants

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Increased Incidence of Major Bleeding in Children Receiving Unfractionated Heparin for Clinical Management: A Prospective Cohort Study.

Blood ◽

10.1182/blood.v104.11.1772.1772 ◽

2004 ◽

Vol 104 (11) ◽

pp. 1772-1772 ◽

Cited By ~ 2

Author(s):

Lesley G. Mitchell ◽

Stefan Kuhle ◽

Patricia M. Massicotte ◽

Patricia Vegh

Keyword(s):

Cohort Study ◽

Unfractionated Heparin ◽

Prospective Cohort Study ◽

Major Bleeding ◽

Prospective Cohort ◽

Recurrent Thrombosis ◽

Heparin Dose ◽

Bleeding Events ◽

Major Bleeding Events ◽

Relationship Of

Abstract BACKGROUND: Unfractionated heparin (UFH) is one of the most frequently prescribed drugs in paediatric tertiary care centres and is used in a diverse group of disorders including cardiopulmonary bypass, extra corporeal membrane oxygenation, dialyses and maintenance of both venous and arterial catheter patency. Dosing of UFH in children is extrapolated from adults and is assessed by either a chromogenic Anti-Xa assay or a clot-based activated partial thromboplastin time (aPTT). The overall objective of the study was to assess safety of current standard of practice in the use of therapeutic UFH in children. Objective #1: The primary objective was to determine the incidence of bleeding and the incidence of recurrent thrombosis in children receiving UFH. Objective #2: To assess the monitoring UFH by assessing the relationship of the aPTT and Anti-Xa heparin levels to heparin dose. STUDY DESIGN: A prospective cohort study in nonselected children in a intensive care setting. The primary outcomes were major bleeding events and recurrent thrombosis. The secondary outcomes were assessing the APTT and Anti-Xa levels. Inclusion Criteria: Patients 〉 36 weeks gestation and 〈18 years of age requiring therapeutic doses of UFH. Exclusion Criteria: patients who received UFH for less than 1 day. Major bleeding was defined aprior as any of the following: CNS bleeding, retroperitoneal bleeding, and/or bleeding that results in stopping UFH infusion. RESULTS: Patient Population 39 patients were enrolled, 22 (56%) male, 32 (82%) < 1 year of age and 90% of which where cardiac patients. Major Bleeding events: 11/39 patients had a major bleeding event 28.2% (95% CI 15.0–44.9%). No patient had recurrent thrombosis. Relationship of aPPT and Anti-Xa to heparin dose; A total of 188 paired aPTTs and anti-Xa levels were performed. There was little correlation between aPTT and anti-Xa levels (r2=0.205) and APTT and UFH dose (r2=0.054). There was no relationship between anti-Xa levels and UFH dose (r2=0.0089). (Figure 1 and 2) Figure Figure CONCLUSIONS:. There is an unacceptably high rate of bleeding in children receiving UFH for clinical care. There is little or no relationship of aPPT and Anti-Xa to heparin dose. Clinical trials are needed to assess the appropriate use of UFH therapy in children.

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Combination Of 4T’s Score and Rapid Gel Centrifugation Assay Excludes HIT In a Prospective Cohort Study

Blood ◽

10.1182/blood.v122.21.3535.3535 ◽

2013 ◽

Vol 122 (21) ◽

pp. 3535-3535 ◽

Cited By ~ 1

Author(s):

Lori Ann Linkins ◽

Shannon M. Bates ◽

Agnes Y.Y. Lee ◽

Theodore E. Warkentin

Keyword(s):

Cohort Study ◽

Prospective Cohort Study ◽

Prospective Cohort ◽

Research Funding ◽

Diagnostic Testing ◽

Prediction Rule ◽

Turnover Time ◽

Serotonin Release ◽

Diagnostic Strategy ◽

Bleeding Events

Abstract The diagnosis of heparin-Induced thrombocytopenia (HIT) is based on the presence of a compatible clinical picture combined with laboratory evidence of heparin-dependent, platelet-activating IgG antibodies. The 4T's Score is a clinical prediction rule that determines the likelihood that a patient has HIT before laboratory testing is performed. A rapid assay (H/PF4-PaGIA, Diamed, Switzerland) uses gel centrifugation to measure binding of antibodies to antigen-coated polystyrene beads (15 min turnover time). The purpose of this study is to evaluate the clinical utility of a diagnostic strategy which combines the 4T's Score with a H/PF4-PaGIA result to guide management of patients with suspected HIT while awaiting results of the serotonin-release assay (SRA). Methods Prospective cohort study of 538 consecutive adult patients with suspected HIT at 4 Canadian hospitals. Physicians completed a standardized 4T's Score sheet and the H/PF4-PaGIA was performed using fresh plasma in a central lab by technologists blinded to the 4T's Score (frozen plasma was used for 85 patients due to disruptions in worldwide availability of the assay.) The SRA and an in-house IgG anti-PF4/H enzyme-immunoassay (EIA) were performed on all patients by blinded technologists. Serologically-confirmed HIT (“HIT positive”) was defined as >50% serotonin release (mean) at three reaction conditions (0.1 U/mL heparin; 0.3 U/mL heparin; enoxaparin, 0.1 U/ml), as well as inhibition (<20% release or >50% inhibition) at 100 U/mL heparin and in the presence of Fc receptor-blocking monoclonal antibody, and a positive EIA. Thrombotic events, major bleeding events, and mortality were captured at day 30. Recommendations for management of patients while awaiting the SRA: patients with a Low 4T's Score (irrespective of H/PF4-PaGIA result) and patients with an Intermediate 4T's Score and negative H/PF4-PaGIA were to receive low-dose danaparoid or fondaparinux. Therapeutic-dose non-heparin anticoagulation was recommended for all patients with an Intermediate 4T's Score and positive H/PF4-PaGIA and for all patients with a High 4T's Score irrespective of H/PF4-PaGIA result. The primary outcome measure was the frequency of management failures defined as a patient with serologically-confirmed HIT who had one of the following combinations of diagnostic testing (a) Low 4T's Score and negative H/PF4-PaGIA; (b) Low 4T's Score and positive H/PF4-PaGIA or (c) Intermediate 4T's Score and negative H/PF4-PaGIA. Results 527 patients with mean age 66.5 yr (sd 15.4) were analyzed; 11 patients with missing diagnostic testing results were excluded. Clinical outcomes of the management of patients according to the diagnostic strategy will be reported separately. Results of diagnostic accuracy of the 4T's Score and H/PF4-PaGIA compared to the SRA are provided below. The prevalence of serologically-confirmed HIT in the study population was 6.5%. Two patients with indeterminate SRAs but IgG>1.0 were reported as HIT Positive. A negative H/PF4-PaGIA result reduced the probability of HIT based on the 4T's Score from 2.5% to 0.7% (95% CI: 0.1-2.6%) in the Low group, from 6.1% to 0% (95% CI: 0-2.7%) in the Intermediate group and from 35.7% to 0% (95% CI: 0-14.3%) in the High group. A positive H/PF4-PaGIA result increased the probability of HIT based on the 4T's Score to 15.4% (Low 4T's), 38.5% (intermediate 4T's) and 83.3% (High 4T's). The proportion of management failures was 1.5% (95% CI : 0.7%-3.0%). Of the 8 patients who were identified as management failures, 2 (Low 4T's) had a negative H/PF4-PaGIA. Out of 33 HIT Positive patients, 8 (24.2%) would have been missed based on a Low 4T's Score alone and 2 (6.1%) based on negative H/PF4-PaGIA alone. The combination of a Low or Intermediate 4T's Score and a negative H/PF4-PaGIA result had a negative predictive value for HIT of 99.5% (95% CI: 98.3-99.9). Conclusions The proportion of management failures was low (1.5%) and within acceptable limits (95% CI : 0.7%-3.0%). Combining the 4T's Score with the result of H/PF4-PaGIA excludes the diagnosis of HIT in the majority of patients with a Low or Intermediate probability for HIT and raises the likelihood of HIT in patients with a High probability. Disclosures: Linkins: BioRad DiaMed: PaGIA assays purchased at cost for study Other. Bates:BioRad Diamed: provided assays for study at cost Other. Lee:BioRad Diamed: provided assays for study at cost Other. Warkentin:GSK: Research Funding; WL Gore: Consultancy; Immucor GTI Diagnostics: Research Funding; Paringenix: Consultancy; Pfizer Canada: Honoraria; BioRad Diamed: provided assays for study at cost, provided assays for study at cost Other.

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