Meta-analysis of statins in chronic kidney disease: who benefits?

Background: Attempts to reduce the burden of vascular disease in advanced chronic kidney disease (CKD) by control of lipids have not been as successful as predicted. Aim: To determine the extent to which the effectiveness of statins varies by kidney class. Design: Meta-analysis. Methods: We selected randomized trials of statin vs. placebo that gave outcomes for CKD3 (eGFR 30–59 ml/min), CKD4 (eGFR 15–29 ml/min), CKD5 (eGFR < 15 ml/min)/5D(dialysis) and transplant patients separately. Data sources were the Cholesterol Triallists’ Treatment Collaboration and previously published meta-analyses. Main outcome measures were major cardiovascular events (MACE), cardiovascular death and all-cause mortality (ACM). Results: A total of 13 studies provided 19 386 participants with CKD3, 2565 with CKD4, 7051 with CKD5/5D and 2102 with a functioning renal transplant. Statins reduced MACE (pooled HR 0.72, 95% CI 0.67–0.78) and ACM (0.82, 0.73–0.91) in CKD3; probably reduced MACE (0.78, 0.62–0.99) in CKD4; and probably reduced cardiovascular death (0.62, 0.40–0.96) in renal transplants. There were no cardiovascular or ACM data in CKD4; there was no convincing evidence of benefit for any outcome in CKD5/5D; and no significant reduction in MACE or ACM in patients with a functioning transplant. Conclusions: Statins are indicated in CKD3, probably indicated in CKD4, not indicated in CKD5/5D and probably indicated in patients with a functioning transplant. Too few patients with CKD4 and renal transplants have been included in lipid lowering trials for confident conclusions to be drawn

A new approach to scoring systems to improve identification of acute medical admissions that will require critical care

Removal of the intensive care unit (ICU) at the Vale of Leven Hospital mandated the identification and transfer out of those acute medical admissions with a high risk of requiring ICU. The aim of the study was to develop triaging tools that identified such patients and compare them with other scoring systems. The methodology included a retrospective analysis of physiological and arterial gas measurements from 1976 acute medical admissions produced PREEMPT-1 (PRE-critical Emergency Medical Patient Triage). A simpler one for ambulance use (PREAMBLE-1 [PRE-Admission Medical Blue-Light Emergency]) was produced by the addition of peripheral oxygen saturation to a modification of MEWS (Modified Early Warning Score). Prospective application of these tools produced a larger database of 4447 acute admissions from which logistic regression models produced PREEMPT-2 and PREAMBLE-2, which were then compared with the original systems and seven other early warning scoring systems. Results showed that in patients with arterial gases, the area under the receiver operator characteristic curve was significantly higher in PREEMPT-2 (89·1%) and PREAMBLE-2 (84.4%) than all other scoring systems. Similarly, in all patients, it was higher in PREAMBLE-2 (92·4%) than PREAMBLE-1 (88·1%) and the other scoring systems. In conclusion, risk of requiring ICU can be more accurately predicted using PREEMPT-2 and PREAMBLE-2, as described here, than by other early warning scoring systems developed over recent years

Study protocol: a randomised controlled trial on the clinical effects of levothyroxine treatment for subclinical hypothyroidism in people aged 80 years and over

Background: Subclinical hypothyroidism is common in older people and its contribution to health and disease needs to be elucidated further. Observational and clinical trial data on the clinical effects of subclinical hypothyroidism in persons aged 80 years and over is inconclusive, with some studies suggesting harm and some suggesting benefits, translating into equipoise whether levothyroxine therapy provides clinical benefits. This manuscript describes the study protocol for the Institute for Evidence-Based Medicine in Old Age (IEMO) 80-plus thyroid trial to generate the necessary evidence base. Methods: The IEMO 80-plus thyroid trial was explicitly designed as an ancillary experiment to the Thyroid hormone Replacement for Untreated older adults with Subclinical hypothyroidism randomised placebo controlled Trial (TRUST) with a near identical protocol and shared research infrastructure. Outcomes will be presented separately for the IEMO and TRUST 80-plus groups, as well as a pre-planned combined analysis of the 145 participants included in the IEMO trial and the 146 participants from the TRUST thyroid trial aged 80 years and over. The IEMO 80-plus thyroid trial is a multi-centre randomised double-blind placebo-controlled parallel group trial of levothyroxine treatment in community-dwelling participants aged 80 years and over with persistent subclinical hypothyroidism (TSH ≥4.6 and ≤ 19.9 mU/L and fT4 within laboratory reference ranges). Participants are randomised to levothyroxine 25 or 50 micrograms daily or matching placebo with dose titrations according to TSH levels, for a minimum follow-up of one and a maximum of three years. Primary study endpoints: hypothyroid physical symptoms and tiredness on the thyroid-related quality of life patient-reported outcome (ThyPRO) at one year. Secondary endpoints: generic quality of life, executive cognitive function, handgrip strength, functional ability, blood pressure, weight, body mass index, and mortality. Adverse events will be recorded with specific interest on cardiovascular endpoints such as atrial fibrillation and heart failure. Discussion: The combined analysis of participants in the IEMO 80-plus thyroid trial with the participants aged over 80 in the TRUST trial will provide the largest experimental evidence base on multimodal effects of levothyroxine treatment in 80-plus persons to date

Study protocol: A randomised controlled trial on the clinical effects of levothyroxine treatment for subclinical hypothyroidism in people aged 80 years and over

Background: Subclinical hypothyroidism is common in older people and its contribution to health and disease needs to be elucidated further. Observational and clinical trial data on the clinical effects of subclinical hypothyroidism in persons aged 80 years and over is inconclusive, with some studies suggesting harm and some suggesting benefits, translating into equipoise whether levothyroxine therapy provides clinical benefits. This manuscript describes the study protocol for the Institute for Evidence-Based Medicine in Old Age (IEMO) 80-plus thyroid trial to generate the necessary evidence base. Methods: The IEMO 80-plus thyroid trial was explicitly designed as an ancillary experiment to the Thyroid hormone Replacement for Untreated older adults with Subclinical hypothyroidism randomised placebo controlled Trial (TRUST) with a ne

Reference range for the antimüllerian hormone Generation II assay: a population study of 10,984 women, with comparison to the established Diagnostics Systems Laboratory nomogram

Objective: To develop an optimal model and age-specific centiles for the decline in antimüllerian hormone (AMH) as measured by the new Beckman Coulter AMH Generation II (Gen II) assay and compare this to the previous nomogram derived for the Diagnostics Systems Laboratory (DSL) assay.<p></p> Design: Multicenter retrospective population study, with validation of linear, biphasic linear, differential, power, and quadratic equations.<p></p> Setting: Two clinical pathology laboratories.<p></p> Patient(s): A new cohort of 10,984 women aged 25 to 45 years old attending infertility clinics, randomly divided into a training cohort of 5,492 women and a validation cohort of 5,492 women, and an existing cohort of 9,601 women, who had contributed to the development and validation of a nomogram for AMH measured by the DSL assay.<p></p> Intervention(s): Serum measurement of AMH as determined by the Beckman Coulter AMH Generation II assay in 10,984 women.<p></p> Main Outcome Measure(s): Optimal model for the decline in AMH as measured by the AMH Gen II assay with age, with age-specific 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles.<p></p> Result(s): A quadratic model defined as (2.431 + 0.089 * Age + −0.003 * Age2) fitted the decline in AMH with age. The anticipated 40% increase in age-specific population values relative to the previously validated DSL assay nomogram was not observed.<p></p> Conclusion(s): Age-specific reference ranges for the AMH gen II assay suggest a systematic shift in assay calibration since initial evaluation and commercial release of the AMH Gen II assay.<p></p&gt

The relationship between anti-Mullerian hormone in women receiving fertility assessments and age at menopause in subfertile women: Evidence from large population studies

Context: Anti-Müllerian hormone (AMH) concentration reflects ovarian aging and is argued to be a useful predictor of age at menopause (AMP). It is hypothesized that AMH falling below a critical threshold corresponds to follicle depletion, which results in menopause. With this threshold, theoretical predictions of AMP can be made. Comparisons of such predictions with observed AMP from population studies support the role for AMH as a forecaster of menopause. Objective: The objective of the study was to investigate whether previous relationships between AMH and AMP are valid using a much larger data set. Setting: AMH was measured in 27 563 women attending fertility clinics. Study Design: From these data a model of age-related AMH change was constructed using a robust regression analysis. Data on AMP from subfertile women were obtained from the population-based Prospect-European Prospective Investigation into Cancer and Nutrition (Prospect- EPIC) cohort (n � 2249). By constructing a probability distribution of age at which AMH falls below a critical threshold and fitting this to Prospect-EPIC menopausal age data using maximum likelihood, such a threshold was estimated. Main Outcome: The main outcome was conformity between observed and predicted AMP. Results: To get a distribution of AMH-predicted AMP that fit the Prospect-EPIC data, we found the critical AMH threshold should vary among women in such a way that women with low age-specific AMH would have lower thresholds, whereas women with high age-specific AMH would have higher thresholds (mean 0.075 ng/mL; interquartile range 0.038–0.15 ng/mL). Such a varying AMH threshold for menopause is a novel and biologically plausible finding. AMH became undetectable (�0.2 ng/mL) approximately 5 years before the occurrence of menopause, in line with a previous report. Conclusions: The conformity of the observed and predicted distributions of AMP supports the hypothesis that declining population averages of AMH are associated with menopause, making AMH an excellent candidate biomarker for AMP prediction. Further research will help establish the accuracy of AMH levels to predict AMP within individuals

The relationship between anti-Mullerian hormone in women receiving fertility assessments and age at menopause in subfertile women: Evidence from large population studies

Context: Anti-Müllerian hormone (AMH) concentration reflects ovarian aging and is argued to be a useful predictor of age at menopause (AMP). It is hypothesized that AMH falling below a critical threshold corresponds to follicle depletion, which results in menopause. With this threshold, theoretical predictions of AMP can be made. Comparisons of such predictions with observed AMP from population studies support the role for AMH as a forecaster of menopause. Objective: The objective of the study was to investigate whether previous relationships between AMH and AMP are valid using a much larger data set. Setting: AMH was measured in 27 563 women attending fertility clinics. Study Design: From these data a model of age-related AMH change was constructed using a robust regression analysis. Data on AMP from subfertile women were obtained from the population-based Prospect-European Prospective Investigation into Cancer and Nutrition (Prospect- EPIC) cohort (n � 2249). By constructing a probability distribution of age at which AMH falls below a critical threshold and fitting this to Prospect-EPIC menopausal age data using maximum likelihood, such a threshold was estimated. Main Outcome: The main outcome was conformity between observed and predicted AMP. Results: To get a distribution of AMH-predicted AMP that fit the Prospect-EPIC data, we found the critical AMH threshold should vary among women in such a way that women with low age-specific AMH would have lower thresholds, whereas women with high age-specific AMH would have higher thresholds (mean 0.075 ng/mL; interquartile range 0.038–0.15 ng/mL). Such a varying AMH threshold for menopause is a novel and biologically plausible finding. AMH became undetectable (�0.2 ng/mL) approximately 5 years before the occurrence of menopause, in line with a previous report. Conclusions: The conformity of the observed and predicted distributions of AMP supports the hypothesis that declining population averages of AMH are associated with menopause, making AMH an excellent candidate biomarker for AMP prediction. Further research will help establish the accuracy of AMH levels to predict AMP within individuals

Association Between Levothyroxine Treatment and Thyroid-Related Symptoms Among Adults Aged 80 Years and Older With Subclinical Hypothyroidism

Cardiolog