Higher Prevalence of "Low T3 Syndrome" in Patients With Chronic Fatigue Syndrome:A Case-Control Study

Chronic fatigue syndrome (CFS) is a heterogeneous disease with unknown cause(s). CFS symptoms resemble a hypothyroid state, possibly secondary to chronic (low-grade) (metabolic) inflammation. We studied 98 CFS patients (21–69 years, 21 males) and 99 age- and sex-matched controls (19–65 years, 23 males). We measured parameters of thyroid function, (metabolic) inflammation, gut wall integrity and nutrients influencing thyroid function and/or inflammation. Most remarkably, CFS patients exhibited similar thyrotropin, but lower free triiodothyronine (FT3) (difference of medians 0.1%), total thyroxine (TT4) (11.9%), total triiodothyronine (TT3) (12.5%), %TT3 (4.7%), sum activity of deiodinases (14.4%), secretory capacity of the thyroid gland (14.9%), 24-h urinary iodine (27.6%), and higher % reverse T3 (rT3) (13.3%). FT3 below the reference range, consistent with the “low T3 syndrome,” was found in 16/98 CFS patients vs. 7/99 controls (OR 2.56; 95% confidence interval = 1.00–6.54). Most observations persisted in two sensitivity analyses with more stringent cutoff values for body mass index, high-sensitive C-reactive protein (hsCRP), and WBC. We found possible evidence of (chronic) low-grade metabolic inflammation (ferritin and HDL-C). FT3, TT3, TT4, and rT3 correlated positively with hsCRP in CFS patients and all subjects. TT3 and TT4 were positively related to hsCRP in controls. Low circulating T3 and the apparent shift from T3 to rT3 may reflect more severely depressed tissue T3 levels. The present findings might be in line with recent metabolomic studies pointing at a hypometabolic state. They resemble a mild form of “non-thyroidal illness syndrome” and “low T3 syndrome” experienced by a subgroup of hypothyroid patients receiving T4 monotherapy. Our study needs confirmation and extension by others. If confirmed, trials with, e.g., T3 and iodide supplements might be indicated

Influence of a 10-Day Mimic of Our Ancient Lifestyle on Anthropometrics and Parameters of Metabolism and Inflammation: The (Study of Origin)

Chronic low-grade inflammation and insulin resistance are intimately related entities that are common to most, if not all, chronic diseases of affluence. We hypothesized that a short-term intervention based on "ancient stress factors" may improve anthropometrics and clinical chemical indices. We executed a pilot study of whether a 10-day mimic of a hunter-gatherer lifestyle favorably affects anthropometrics and clinical chemical indices. Fifty-five apparently healthy subjects, in 5 groups, engaged in a 10-day trip through the Pyrenees. They walked 14 km/day on average, carrying an 8-kilo backpack. Raw food was provided and self-prepared and water was obtained from waterholes. They slept outside in sleeping bags and were exposed to temperatures ranging from 12 to 42 ∘ C. Anthropometric data and fasting blood samples were collected at baseline and the study end. We found important significant changes in most outcomes favoring better metabolic functioning and improved anthropometrics. Coping with "ancient mild stress factors," including physical exercise, thirst, hunger, and climate, may influence immune status and improve anthropometrics and metabolic indices in healthy subjects and possibly patients suffering from metabolic and immunological disorders

The sedentary (r)evolution:Have we lost our metabolic flexibility?

During the course of evolution, up until the agricultural revolution, environmental fluctuations forced the human species to develop a flexible metabolism in order to adapt its energy needs to various climate, seasonal and vegetation conditions. Metabolic flexibility safeguarded human survival independent of food availability. In modern times, humans switched their primal lifestyle towards a constant availability of energy-dense, yet often nutrient-deficient, foods, persistent psycho-emotional stressors and a lack of exercise. As a result, humans progressively gain metabolic disorders, such as the metabolic syndrome, type 2 diabetes, non-alcoholic fatty liver disease, certain types of cancer, cardiovascular disease and Alzheimer´s disease, wherever the sedentary lifestyle spreads in the world. For more than 2.5 million years, our capability to store fat for times of food shortage was an outstanding survival advantage. Nowadays, the same survival strategy in a completely altered surrounding is responsible for a constant accumulation of body fat. In this article, we argue that the metabolic epidemic is largely based on a deficit in metabolic flexibility. We hypothesize that the modern energetic inflexibility, typically displayed by symptoms of neuroglycopenia, can be reversed by re-cultivating suppressed metabolic programs, which became obsolete in an affluent environment, particularly the ability to easily switch to ketone body and fat oxidation. In a simplified model, the basic metabolic programs of humans’ primal hunter-gatherer lifestyle are opposed to the current sedentary lifestyle. Those metabolic programs, which are chronically neglected in modern surroundings, are identified and conclusions for the prevention of chronic metabolic diseases are drawn

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

The sedentary (r)evolution: Have we lost our metabolic flexibility? [version 2; referees: 2 approved, 1 approved with reservations]

During the course of evolution, up until the agricultural revolution, environmental fluctuations forced the human species to develop a flexible metabolism in order to adapt its energy needs to various climate, seasonal and vegetation conditions. Metabolic flexibility safeguarded human survival independent of food availability. In modern times, humans switched their primal lifestyle towards a constant availability of energy-dense, yet often nutrient-deficient, foods, persistent psycho-emotional stressors and a lack of exercise. As a result, humans progressively gain metabolic disorders, such as the metabolic syndrome, type 2 diabetes, non-alcoholic fatty liver disease, certain types of cancer, cardiovascular disease and Alzheimer´s disease, wherever the sedentary lifestyle spreads in the world. For more than 2.5 million years, our capability to store fat for times of food shortage was an outstanding survival advantage. Nowadays, the same survival strategy in a completely altered surrounding is responsible for a constant accumulation of body fat. In this article, we argue that the metabolic disease epidemic is largely based on a deficit in metabolic flexibility. We hypothesize that the modern energetic inflexibility, typically displayed by symptoms of neuroglycopenia, can be reversed by re-cultivating suppressed metabolic programs, which became obsolete in an affluent environment, particularly the ability to easily switch to ketone body and fat oxidation. In a simplified model, the basic metabolic programs of humans’ primal hunter-gatherer lifestyle are opposed to the current sedentary lifestyle. Those metabolic programs, which are chronically neglected in modern surroundings, are identified and conclusions for the prevention of chronic metabolic diseases are drawn

Corrigendum to "Influence of a 10-Day Mimic of Our Ancient Lifestyle on Anthropometrics and Parameters of Metabolism and Inflammation: The "Study of Origin""

[This corrects the article DOI: 10.1155/2016/6935123.]

Influence of a 10-Day Mimic of Our Ancient Lifestyle on Anthropometrics and Parameters of Metabolism and Inflammation: The “Study of Origin”

Chronic low-grade inflammation and insulin resistance are intimately related entities that are common to most, if not all, chronic diseases of affluence. We hypothesized that a short-term intervention based on “ancient stress factors” may improve anthropometrics and clinical chemical indices. We executed a pilot study of whether a 10-day mimic of a hunter-gatherer lifestyle favorably affects anthropometrics and clinical chemical indices. Fifty-five apparently healthy subjects, in 5 groups, engaged in a 10-day trip through the Pyrenees. They walked 14 km/day on average, carrying an 8-kilo backpack. Raw food was provided and self-prepared and water was obtained from waterholes. They slept outside in sleeping bags and were exposed to temperatures ranging from 12 to 42°C. Anthropometric data and fasting blood samples were collected at baseline and the study end. We found important significant changes in most outcomes favoring better metabolic functioning and improved anthropometrics. Coping with “ancient mild stress factors,” including physical exercise, thirst, hunger, and climate, may influence immune status and improve anthropometrics and metabolic indices in healthy subjects and possibly patients suffering from metabolic and immunological disorders

To Restore Health, “Do we Have to Go Back to the Future?” The Impact of a 4-Day Paleolithic Lifestyle Change on Human Metabolism – a Pilot Study.

On their way from the Stone Age via the Agricultural Revolution to current high-tech conditions, humans lost their primal foraging behavior. Today, energy expenditure is not necessary anymore for gathering nor hunting, and metabolic diseases are epidemically arising wherever our original Paleolithic lifestyle is turning into a modern sedentary lifestyle. In this pilot study, we followed through the concept that a radical change towards a Paleolithic hunter-gatherer lifestyle could serve as therapy against any metaflammatory disease, even in the short term. Thirteen healthy adult volunteers were transferred to the DELUX National Park (Germany and Luxembourg) for four days and three nights, where Stone Age conditions where mimicked. Thirty-eight biochemical and bioelectrical parameters were measured from participants before and after this relocation. Body weight (-3,9%), body fat (-7,5%), body mass index (-3,8%), visceral fat area (-14,4%) and metaflammation-related parameters (fasting glucose = -18,2%; fasting insulin = -50,1%; HOMA = -57,8%) decreased significantly. C-reactive protein, as the main indicator for low-grade inflammation, increased up to an average of 169,6 %. Our data show that returning to our Paleolithic roots may have positive effects on risk factors commonly associated with metabolic disorders, such as obesity and type 2 diabetes. These findings may lead the way to further research to answer the question whether the already existing metabolic conditions and/or autoimmune and neuroinflammatory diseases could be influenced by a Paleolithic lifestyle