Substantial and sustained improvements in blood pressure, weight and lipid profiles from a carbohydrate restricted diet: an observational study of insulin resistant patients in primary care

Hypertension is the second biggest known global risk factor for disease after poor diet; perhaps lifestyle interventions are underutilized? In a previous small pilot study, it was found that a low carbohydrate diet was associated with significant improvements in blood pressure, weight, ‘deprescribing’ of medications and lipid profiles. We were interested to investigate if these results would be replicated in a larger study based in ‘real world’ GP practice. 154 patients with type 2 diabetes or impaired glucose tolerance were recruited into an observational cohort study in primary care. The effects of a low carbohydrate diet sustained for an average of two years (interquartile range 10–32 months) on cardiovascular risk factors were examined. Results demonstrate significant and substantial reductions in blood pressure (mean reduction of systolic BP 10.9 mmHg (interquartile range 0–22 mmHg) (p < 0.0001), mean reduction in diastolic BP 6.3 mmHg (interquartile range 0–12.8 mmHg) (p < 0.0001) and mean weight reduction of 9.5 Kg (interquartile range 5–13 Kg) (p < 0.0001) together with marked improvement in lipid profiles. This occurred despite a 20% reduction in anti-hypertensive medications. This novel and potentially highly effective dietary modification, done very cheaply alongside routine care, offers hope that should be tested in a large prospective trial

Aspirin and cancer survival: a systematic review and meta-analyses of 118 observational studies of aspirin and 18 cancers.

BackgroundDespite the accumulation of research papers on aspirin and cancer, there is doubt as to whether or not aspirin is an acceptable and effective adjunct treatment of cancer. The results of several randomised trials are awaited, and these should give clear evidence on three common cancers: colon, breast and prostate. The biological effects of aspirin appear likely however to be of relevance to cancer generally, and to metastatic spread, rather than just to one or a few cancers, and there is already a lot of evidence, mainly from observational studies, on the association between aspirin and survival in a wide range of cancers.AimsIn order to test the hypothesis that aspirin taking is associated with an increase in the survival of patients with cancer, we conducted a series of systematic literature searches to identify clinical studies of patients with cancer, some of whom took aspirin after having received a diagnosis of cancer.ResultsThree literature searches identified 118 published observational studies in patients with 18 different cancers. Eighty-one studies report on aspirin and cancer mortality and 63 studies report on all-cause mortality. Within a total of about a quarter of a million patients with cancer who reported taking aspirin, representing 20%-25% of the total cohort, we found aspirin to be associated with a reduction of about 20% in cancer deaths (pooled hazard ratio (HR): 0.79; 95% confidence intervals: 0.73, 0.84 in 70 reports and a pooled odds ratio (OR): 0.67; 0.45, 1.00 in 11 reports) with similar reductions in all-cause mortality (HR: 0.80; 0.74, 0.86 in 56 studies and OR: 0.57; 0.36, 0.89 in seven studies). The relative safety of aspirin taking was examined in the studies and the corresponding author of every paper was written to asking for additional information on bleeding. As expected, the frequency of bleeding increased in the patients taking aspirin, but fatal bleeding was rare and no author reported a significant excess in fatal bleeds associated with aspirin. No author mentioned cerebral bleeding in the patients they had followed.ConclusionsThere is a considerable body of evidence suggestive of about a 20% reduction in mortality in patients with cancer who take aspirin, and the benefit appears not to be restricted to one or a few cancers. Aspirin, therefore, appears to deserve serious consideration as an adjuvant treatment of cancer, and patients with cancer, and their carers, have a right to be informed of the available evidence

Optimization of Unrelated Donor Cord Blood Transplantation for Thalassemia: Implications for Other Non‐Malignant Indications such as HIV Infection or Autoimmune Diseases

Since the first cord blood transplantation (CBT), many indications have been proven for this stem cell therapy. Besides the standard hematological indications, such as leukemia, lymphomas, and aplastic anemia, CBT has also been a proven curative therapy for non-hematological indications such as Krabbe’s disease, and osteopetrosis. As transplant-related mortality (TRM), overall survival (OS) and disease-free survival (DFS) for CBT continue to improve with larger inventories, double CBT, higher cell dose CB products, optimal conditioning, GvHD, HLA matching, and infection prophylaxis and treatment, the utility of this stem cell source will expand to certain indications which in the past, rarely used CBT. For patients and physicians to accept CBT for indications such as thalassemia, autoimmune diseases or HIV, the benefit-risk ratio has to be significantly improved so that patients will take a chance on a risky procedure in order to improve their lifespan or quality of life. We review here some of the efforts to improve clinical outcome of CBT for thalassemia through increasing cell dosage using a combination strategy – (1) Chow’s MaxCell second and third generation technologies that maximize CB cell dosage, (2) double CBT, (3) no-wash thaw direct infusion advocated by Chow et al., and (4) optimal product selection

Aspirin and cancer: biological mechanisms and clinical outcomes

Evidence on aspirin and cancer comes from two main sources: (1) the effect of aspirin upon biological mechanisms in cancer, and (2) clinical studies of patients with cancer, some of whom take aspirin. A series of systematic literature searches identified published reports relevant to these two sources. The effects of aspirin upon biological mechanisms involved in cancer initiation and growth appear to generate reasonable expectations of effects upon the progress and mortality of cancer. Clinical evidence on aspirin appears overall to be favourable to the use of aspirin, but evidence from randomized trials is limited, and inconsistent. The main body of evidence comes from meta-analyses of observational studies of patients with a wide range of cancers, about 25% of whom were taking aspirin. Heterogeneity is large but, overall, aspirin is associated with increases in survival and reductions in metastatic spread and vascular complications of different cancers. It is important that evaluations of aspirin used as an adjunct cancer treatment are based upon all the available relevant evidence, and there appears to be a marked harmony between the effects of aspirin upon biological mechanisms and upon the clinical progress of cancer

Cord Blood Stem Cell Processing, Banking and Thawing

Unrelated donor cord blood (CB) is one of the three sources of hematopoietic stem cell transplantation (HSCT) that are capable of curing ~80–160 standard hematologic and certain non-hematologic indications. Despite its many advantages, the principal drawback for CB in HSCT is its limited cell dose. Our group has focused on developing minimally manipulated technologies and strategies to maximize stem, progenitor, and nucleated cell doses to overcome this limitation. The term “MaxCell” is used in this chapter to denote two proprietary CB volume reduction processing technologies that yield virtually 100% recovery of all cell lineages in the manufactured CB products, including what the authors designate as “second generation” (2nd Gen) or plasma depletion/reduction (PDR) and “third generation” (3rd Gen) MaxCB or MaxCord CB processing technologies. In our proposed nomenclature system, the traditional red cell reduction (RCR) processing techniques are designated as “first generation” methods. The properties of various popular 1st Gen techniques are compared to the MaxCell CB processing technologies. Parallel processing with the traditional hetastarch (HES) RCR technique and the patented MaxCell CB processing technology were used to compare recovery of the various stem, progenitor, nucleated, and red cell lineages. MaxCell processing technology achieved virtually 100% recovery of all stem, progenitor, and nucleated cells tested after processing, with high cell viability upon thawing. The higher cell recovery produced MaxCell inventory with higher average stem, progenitor and nucleated cell doses, allowing patients to receive CB products with higher cell doses. Clinical outcome of HSCT using MaxCell CB products was compared to the outcome of HSCT with RCR CB products published in the literature from transplant data registries or CB banks. To allow for more rigorous comparisons, two matched-pair analysis (MP) were performed using a logistic regression model to find pairs of pediatric patients with hematologic malignancies and thalassemia transplanted with RCR CB or MaxCell CB, and patients receiving MaxCell CB showed superior engraftment, survival, and transplant-related mortality, confirming pre-match observations

Insights from a general practice service evaluation supporting a lower carbohydrate diet in patients with type 2 diabetes mellitus and prediabetes: a secondary analysis of routine clinic data including HbA1c, weight and prescribing over 6 years.

BACKGROUND: In a single general practice (GP) surgery in England, there was an eightfold increase in the prevalence of type 2 diabetes (T2D) in three decades with 57 cases and 472 cases recorded in 1987 and 2018, respectively. This mirrors the growing burden of T2D on the health of populations round the world along with healthcare funding and provision more broadly. Emerging evidence suggests beneficial effects of carbohydrate-restricted diets on glycaemic control in T2D, but its impact in a 'real-world' primary care setting has not been fully evaluated. METHODS: Advice on a lower carbohydrate diet was offered routinely to patients with newly diagnosed and pre-existing T2D or prediabetes between 2013 and 2019, in the Norwood GP practice with 9800 patients. Conventional 'one-to-one' GP consultations were used, supplemented by group consultations, to help patients better understand the glycaemic consequences of their dietary choices with a particular focus on sugar, carbohydrates and foods with a higher Glycaemic Index. Those interested were computer coded for ongoing audit to compare 'baseline' with 'latest follow-up' for relevant parameters. RESULTS: By 2019, 128 (27%) of the practice population with T2D and 71 people with prediabetes had opted to follow a lower carbohydrate diet for a mean duration of 23 months. For patients with T2D, the median (IQR) weight dropped from of 99.7 (86.2, 109.3) kg to 91.4 (79, 101.1) kg, p<0.001, while the median (IQR) HbA1c dropped from 65.5 (55, 82) mmol/mol to 48 (43, 55) mmol/mol, p<0.001. For patients with prediabetes, the median (IQR) HbA1c dropped from 44 (43, 45) mmol/mol to 39 (38, 41) mmol/mol, p<0.001. Drug-free T2D remission occurred in 46% of participants. In patients with prediabetes, 93% attained a normal HbA1c. Since 2015, there has been a relative reduction in practice prescribing of drugs for diabetes leading to a T2D prescribing budget £50 885 per year less than average for the area. CONCLUSIONS: This approach to lower carbohydrate dietary advice for patients with T2D and prediabetes was incorporated successfully into routine primary care over 6 years. There were statistically significant improvements in both groups for weight, HbA1c, lipid profiles and blood pressure as well as significant drug budget savings. These results suggest a need for more empirical research on the effects of lower carbohydrate diet and long-term glycaemic control while recording collateral impacts to other metabolic health outcomes

Aspirin and cancer treatment: systematic reviews and meta-analyses of evidence: for and against

Aspirin as a possible treatment of cancer has been of increasing interest for over 50 years, but the balance of the risks and benefits remains a point of contention. We summarise the valid published evidence ‘for’ and ‘against’ the use of aspirin as a cancer treatment and we present what we believe are relevant ethical implications. Reasons for aspirin include the benefits of aspirin taken by patients with cancer upon relevant biological cancer mechanisms. These explain the observed reductions in metastatic cancer and vascular complications in cancer patients. Meta-analyses of 118 observational studies of mortality in cancer patients give evidence consistent with reductions of about 20% in mortality associated with aspirin use. Reasons against aspirin use include increased risk of a gastrointestinal bleed though there appears to be no valid evidence that aspirin is responsible for fatal gastrointestinal bleeding. Few trials have been reported and there are inconsistencies in the results. In conclusion, given the relative safety and the favourable effects of aspirin, its use in cancer seems justified, and ethical implications of this imply that cancer patients should be informed of the present evidence and encouraged to raise the topic with their healthcare team

Une famille d'épistoliers des Lumières (Les Roux de Laric)

Les 3000 lettres des Roux de Laric, intégrées dans un fonds d'archives familiales inédit, permet une lecture croisée de différentes formes d'écrits et leur mise en relation. Parlementaires au service du roi, partisans de la réforme Maupeou, les Laric quittent ensuite la robe pour l'épée dans un souci de diversifier les voies de la réussite. Soucieux de s'intégrer aux élites, ils s'approchent enfin des cercles de pouvoir, après trois générations d'une ascension sociale réussie.Cette correspondance permet de cerner comment les épistoliers vivent leur époque et la comprennent, offrant une image d'un monde en devenir, partagés entre le poids de l'héritage féodal et la découverte de nouvelles valeurs: le goût du plaisir et du confort ou le libertinage par exemple. Le rôle de l'écrit apparaît comme dominant et la noblesse provinciale diffuse jusque dans les marches du royaume les ouvrages autorisés ou clandestins, imprimés et manuscrits. L'analyse des titres de leur bibliothèque montre des lecteurs classiques, dont les goûts se figent à la Révolution.Cette correspondance doit être lue enfin comme un témoignage d'écriture épistolaire, entre respect des normes et créativité. Formés par l'éducation des élites, les Laric maitrisent la bienséance épistolaire et s'en écartent pour créer de nouvelles relations familiales ou sociales. Leurs échanges forment enfin une stratégie de réseau, un réseau familial qui s'intègre dans le réseau du monde économique des Lumières. La lettre est au service d'une stratégie.Cette étude cerne donc les multiples facettes d'une correspondance des Lumières, sans en négliger l'inventivité littéraire.The correspondance of the family of Laric, consisting of about 3000 letters, written between1710 and 1780, is integrated into the family archives, permitting cross reading and a comparison of different forms of texts.A presentation of the letter-writers remind us of their role as parlemantarians in the King's service, partisans of the Maupeou reform in Navarre, Provence and the Dauphiné. This dynasty of parlementarians then abandonned the goan for the sword, wishing to diversify their successes. Headful of integrating themselves among the elite, the Laric adopted a strategy of social ascension, which allowed them, after three generations, to approch the circles of power. This corrrespondance enables us to grasp how the epistolers lived and understood the age in which they lived. We are offered an image of a changing world, split between the weight of aristocratic heritage and the discovery of new values. The written word was dominant at the time and the provincial nobility, frequenting Paris, diffused authorisez or secret work through the Kingdom.This correspondance must be read respectin epistolarity style and, indeed, creativity. The Laris, accustomed to the culture of the elite classes, were familiar with epistolary formality, and quickly foresook it in order to create new family or social relationships, ans develop a new style of writing. Their exchanges were intended to form a network strategy in the world of entreprise business : the letter served to fulfill an ambition. This study embraces, therefore, the numerous uses of correspondance in the world of Enlightenment, without neglecting litterary innovations.PARIS4-BU Serpente (751052129) / SudocSudocFranceF