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A patient request for some "deprescribing"
Abstract
A 52 year old man with a history of type 2 diabetes for 14 years and hypertension for nine years presented to his general practitioner. He was a non-smoker with an alcohol intake of eight units a week. He had been experiencing bloating, abdominal pains, and erratic motions for more than a year. Because he drove about 12 000 miles a year for his job he found the loose motions “a real worry.” He wondered whether any of his problems might be caused by his drugs and asked if he could cut down on any if they weren’t all needed. He admitted to being afraid that his diabetic control might deteriorate and that he might need insulin, like some of his relatives who also had diabetes.
He was taking aspirin 75 mg once daily, metformin 500 mg three times daily, perindopril 4 mg daily, and simvastatin 40 mg at night.
On examination his weight was 108.8 kg (steady at this for 10 years), body mass index was 34.4, waist circumference was 113 cm, and his blood pressure was 130/80 mm Hg (steady at this level for some years). His abdominal examination was normal, except that he had central obesity.
Glycated haemoglobin (HbA1c) was 52 mmol/mol (reference range 0-41), bilirubin was 7 µmol/L (0-20), alanine aminotransferase was 53 U/L (5-37), and γ-glutamyl transferase (GGT) was 59 U/L (0-50). In addition, his estimated glomerular filtration rate was 100 mL/min/1.73m2 (90-120), total cholesterol was 3.7 mmol/L (desirable ≤4.0), high density lipoprotein-cholesterol was 1.3 mmol/L (>1.0), and triglycerides were 1.3 mmol/L (<1.7).
... As recently revealed in an openlabel Diabetes Remission Clinical Trial, calorie restriction and weight loss are crucial determinants in T2D remission (DiRECT). However, very few studies or examples of therapeutic fasting as a cure for T2D have been documented or published so far [71]. ...
... Within a month, all three patients were successful, one in as little as five days. In addition, all patients saw improvements in a variety of clinically important health outcomes, including HbA1C, BMI, and waist circumference [71]. This decrease in risk factors will almost certainly lower the likelihood of subsequent difficulties. ...
Diabetes mellitus is a prevalent, life-threatening, and costly medical illness. Type 2 diabetes is defined by insulin resistance caused by persistent hyperglycemia, and it is frequently diagnosed by tests such as fasting blood glucose levels of more than 7.0 mmol/L or HbA1c values of more than 6.5%. Pathogenesis and development of type 2 diabetes mellitus are clearly varied, with genetic and environmental factors both leading to it. The attainment of glycated hemoglobin (HbA1c) levels below the diagnostic level and maintaining it for a minimum of six months without pharmacotherapy, is described as diabetes remission. Diagnosis is a two-part procedure. To begin, the diagnosis of diabetes must be confirmed, and then the type of diabetes must be determined. Even in patients who succeeded to maintain remission, follow-up with the physician and regular tests should be done to prevent any expected diabetes complications.
... Following a low-carbohydrate diet, the patient steadily lost a total of 16 kg over 7 months and successfully stopped all prescribed drugs, thereby achieving his goal of being medication-free. [19] 2-OMEX lifestyle modification also has a regimen with low carbohydrate; however, the benefit of this diet is that it restricts the direct sugar intake. The patient is allowed to eat complex carbohydrates because carbohydrates form the major building blocks, and are also required for the metabolism of various micronutrients, and restricting them completely would lead to their deficiency. ...
A 45-year-old male, resident of Texas, U.S.A, was diagnosed with type-2 diabetes mellitus on September 05, 2020 with HbA1c 14.9%. His physician prescribed oral hypoglycemic agents (OHA) starting immediately due to his high HbA1c levels. However, the patient was reluctant to be on lifelong medications. Thus, he chose conservative management of lifestyle modification by enrolling in “World free of Obesity and Diabetes” campaign that advised “only two meals a day and exercise” regime for diabetes reversal. He followed the plan very meticulously and his HbA1c was successfully reduced by 9.8% (HbA1c from 14.9% to 5.1%) within 3 months without any medications. The patient follows the regime without any burden of compromising his quality of life and has maintained his HbA1c to 4.6% till April 2021. Diabetes reversal by lifestyle modification is a healthier option, and must be encouraged in all the patients in prediabetes group (HbA1c: 5.7%–6.4%) and those with newly diagnosed type 2 diabetes mellitus (HbA1c: >6.5%) without any complications, thus promoting good health-seeking behavior. American Diabetes Association (ADA) suggests that metformin should be started to the prediabetes and newly diagnosed group of patients along with lifestyle modifications. However, there are evidences of complete diabetes reversal of the patients with HbA1c ranging from 8%–15% by just lifestyle modification and that too without any complications among the patients registered under “World free of obesity and diabetes” campaign, which challenges the current prescribed guidelines for the management of type 2 diabetes mellitus.
... While several weight-loss diets can help with fatty liver, this review will discuss studies showing that LCHF diets may be more helpful than Low-Fat High-Carbohydrate calorierestricted diets. While weight loss is effective for reducing liver fat content, there is evidence that the benefits of LCHF diets on this front may be-at least, to some extent-independent of it (Gepner et [7,9,11,17,38] . Moreover, significant improvements may be achieved through carbohydrate restriction rather than calorie restriction alone (Browning et al., 2011;Holmer et al., 2021) [4,11] . ...
This study aims to equip health professionals with essential directions for their practice and research in fatty liver disease. In fatty liver disease, excess fat is accumulated in the liver cells, and it mainly has two types: Alcoholic Fatty Liver Disease (AFLD) and Non-Alcoholic Fatty Liver Disease (NAFLD). AFLD is widely accepted to be associated with excessive alcohol consumption. However, in NAFLD's case, although the name acknowledges that it is not associated with excessive alcohol consumption, the exact cause of NAFLD remains ambiguous. Furthermore, for almost four decades, without specialised treatments and prevention strategies, NAFLD has constantly increased, affecting more than a quarter of the world's population. Meanwhile, although the current dietary recommendations for NAFLD patients orbit around the conventional High-Carbohydrate Low-Fat diets, mounting evidence advocates the broader benefits of Low-Carbohydrate High-Fat (LCHF) diets in this regard.
Therefore, focusing on the databases such as PubMed, Cochrane Library, and Google Scholar, the authors have carried out an advanced literature search reporting on the efficacy of LCHF diets on NAFLD. After a comprehensive search—using appropriate "keywords and Boolean operators" and "inclusion & exclusion criteria"—the authors selected a potentially relevant set of existing peer-reviewed articles for this narrative review. After critically investigating the LCHF-NAFLD theme, the authors found that LCHF diets may significantly decrease liver fat and may even reverse the disease by targeting the key causes of hepatic fat storage, i.e., high insulin levels, excessive calorie consumption (mainly from carbohydrates), and excessive consumption of refined carbohydrates. Additionally, LCHF diets may provide a comprehensive health benefit beyond liver health. The authors conclude that the LCHF- NAFLD theme represents a rich vein of research opportunities. The authors encourage and call researchers, doctors, nutritionists, dieticians, and related-health professionals to engage more with the LCHF-NAFLD theme.
... • Reduced hepatic fat storage-Elevated fat storage in the liver is a key driver of Type 2 diabetes (59), with hyperinsulinaemia and excess energy intake thought to be causative in the development of hepatic fat accumulation (60,61). Although weight loss can be effective for reducing liver fat content, there is evidence that the benefits of LCDs on this front may be, at least in part, independent of this (62)(63)(64)(65); ...
Although carbohydrate restriction is not a new approach for the management of Type 2 diabetes, interest in its safety and efficacy has increased significantly in recent years. The purpose of the current narrative review is to summarise the key relevant research and practical considerations in this area, as well as to explore some of the common concerns expressed in relation to the use of such approaches. There is a strong physiological rationale supporting the role of carbohydrate restriction for the management of Type 2 diabetes, and available evidence suggests that low carbohydrate dietary approaches (LCDs) are as effective as, or superior to, other dietary approaches for its management. Importantly, LCDs appear to be more effective than other dietary approaches for facilitating a reduction in the requirement for certain medications, which leads to their effects on other health markers being underestimated. LCDs have also been demonstrated to be an effective method for achieving remission of Type 2 diabetes for some people. The available evidence does not support concerns that LCDs increase the risk of cardiovascular disease, that such approaches increase the risk of nutrient deficiencies, or that they are more difficult to adhere to than other dietary approaches. A growing number of organisations support the use of LCDs as a suitable choice for individuals with Type 2 diabetes.
... Showcasing n=1 cases may also provide motivation to colleagues, helping them to challenge preconceived ideas and consider the difference between research and clinical practice, then to think through and apply similar approaches to help their own patients-ultimately leading to better practice. 4 However, these views are not dichotomous, but complementary, whereby practice should inform science and science should inform practice. ...
... Campaigners have also highlighted that, for some patients, behavioural change may be a reasonable alternative to medications, and more in line with patient preferences (e.g. Unwin and Tobin 2015). Within this discursive terrain, although CG181 was developed in response to evidence about statins, it also strongly advocates both the promotion of behavioural change, and the principles of patient involvement, shared decision-making and patient-centred care-all of which emphasise the importance of patients' values and preferences in good-quality care. ...
In this article, we draw on an institutional ethnographic (IE) study of cardiovascular disease prevention in general practice, exploring the work of healthcare professionals who introduce a discussion of risk and preventative medications into consultations with patients. Our aim is to explicate, using IE's theoretical ontology and analytical tools, how troubling patient experiences in this clinical context are coordinated institutionally. We focus our attention on the social organisation of healthcare professionals’ knowledge and front‐line practices, highlighting the textual processes through which they overrule patients’ concerns and uncertainties about taking preventative medication, such that some patients feel unable to openly discuss their health needs in preventative consultations. We show how healthcare professionals activate knowledge of ‘evidence‐based risk reduction’ to frame patients’ queries as ‘barriers’ to be overcome. Our analysis points not to deficiencies of healthcare professionals who lack the expertise or inclination to adequately ‘share decisions’ with patients, but to the ways in which their work is institutionally orientated towards performance measures which will demonstrate to local and national policymakers that they are tackling the ‘burden of (cardiovascular) disease’.
... In another randomised weight intervention trial, Mayer et al. reported that weight loss among subjects undertaking either a low-carb or a low-fat diet was similar, but those on a low-carb diet also benefited from an improved glycaemic control and a significant antiglycemic drug dose reduction [7]. Similar reports of "deprescribing" antidiabetic medications have been reported in patients with type 2 diabetes undertaking intensive lifestyle change programs [12]. ...
Subjects diagnosed with non-alcoholic fatty liver disease (NAFLD) or hepatic steatosis are usually obese or overweight. NAFLD has also been reported in many non-obese healthy subjects as an incidental finding during imaging. Subjects with early-stage NAFLD who are otherwise healthy are often left unmanaged in current clinical practice; it is not clear if an early intervention in those individuals would be of any benefit in preventing NAFLD progression to more serious conditions. Since many of these subjects are non-alcoholic and have a normal body mass index (BMI), an intensive lifestyle change program is not usually recommended. This report presents an otherwise healthy non-alcoholic subject with incidental NAFLD having a normal BMI and a waist circumference below 90 cm who successfully reversed his condition by undertaking a lifestyle intervention. The case report is expected to encourage large cohort studies to substantiate the benefits of dietary interventions in alleviating hepatic steatosis among non-obese individuals.
The incidence of diabetes varies strikingly by geographical regions and is rising by 2‐4 percent each year. Although there are many forms of diabetes in childhood and adolescence, type 1 diabetes remains the commonest form. The significant acute complications of type 1 diabetes still occur commonly despite numerous changes in therapy. The association, however, between a lower glycosylated haemoglobin and increased rates of severe hypoglycaemia appears to be no longer present. There are a variety of insulin regimens that are all effective in the treatment of type 1 diabetes. Type 2 diabetes in children and adolescents is largely limited to at risk ethnic groups and, despite the obesity epidemic in children, remains less common than other forms of diabetes in most ethnically mixed populations. There are numerous forms of monogenic diabetes and although uncommon, these should be suspected in individuals who do not have markers of autoimmunity and have a family history or early‐onset diabetes.
This case series documents three patients referred to the Intensive Dietary Management clinic in Toronto, Canada, for insulin-dependent type 2 diabetes. It demonstrates the effectiveness of therapeutic fasting to reverse their insulin resistance, resulting in cessation of insulin therapy while maintaining control of their blood sugars. In addition, these patients were also able to lose significant amounts of body weight, reduce their waist circumference and also reduce their glycated haemoglobin level.
#### Summary points
Non-alcoholic fatty liver disease (NAFLD) is now more common than alcoholic liver disease owing to the rapid rise in the prevalence of obesity,1 and NAFLD is the most common cause of abnormal liver function tests.2 Its prevalence worldwide is thought to be approximately 20% in the general population and up to 70% in patients with type 2 diabetes mellitus.3 The first recognisable stage of NAFLD is hepatic steatosis, when fat content exceeds 5% of liver volume. Simple steatosis is usually benign in terms of risk of progression to …
It has become widely accepted that type 2 diabetes is inevitably life-long, with irreversible and progressive beta cell damage. However, the restoration of normal glucose metabolism within days after bariatric surgery in the majority of people with type 2 diabetes disproves this concept. There is now no doubt that this reversal of diabetes depends upon the sudden and profound decrease in food intake, and does not relate to any direct surgical effect. The Counterpoint study demonstrated that normal glucose levels and normal beta cell function could be restored by a very low calorie diet alone. Novel magnetic resonance methods were applied to measure intra-organ fat. The results showed two different time courses: a) resolution of hepatic insulin sensitivity within days along with a rapid fall in liver fat and normalisation of fasting glucose levels; and b) return of normal beta cell insulin secretion over weeks in step with a fall in pancreas fat. Now that it has been possible to observe the pathophysiological events during reversal of type 2 diabetes, the reverse time course of events which determine the onset of the condition can be identified. The twin cycle hypothesis postulates that chronic calorie excess leads to accumulation of liver fat with eventual spill over into the pancreas. These self-reinforcing cycles between liver and pancreas eventually cause metabolic inhibition of insulin secretion after meals and onset of hyperglycaemia. It is now clear that Type 2 diabetes is a reversible condition of intra-organ fat excess to which some people are more susceptible than others. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.
The UK Prospective Diabetes Study showed that metformin decreases mortality compared to diet alone in overweight patients with type 2 diabetes mellitus. Since then, it has been the first-line treatment in overweight patients with type 2 diabetes. However, metformin-sulphonylurea bitherapy may increase mortality.
This meta-analysis of randomised controlled trials evaluated metformin efficacy (in studies of metformin versus diet alone, versus placebo, and versus no treatment; metformin as an add-on therapy; and metformin withdrawal) against cardiovascular morbidity or mortality in patients with type 2 diabetes. We searched Medline, Embase, and the Cochrane database. Primary end points were all-cause mortality and cardiovascular death. Secondary end points included all myocardial infarctions, all strokes, congestive heart failure, peripheral vascular disease, leg amputations, and microvascular complications. Thirteen randomised controlled trials (13,110 patients) were retrieved; 9,560 patients were given metformin, and 3,550 patients were given conventional treatment or placebo. Metformin did not significantly affect the primary outcomes all-cause mortality, risk ratio (RR)=0.99 (95% CI: 0.75 to 1.31), and cardiovascular mortality, RR=1.05 (95% CI: 0.67 to 1.64). The secondary outcomes were also unaffected by metformin treatment: all myocardial infarctions, RR=0.90 (95% CI: 0.74 to 1.09); all strokes, RR=0.76 (95% CI: 0.51 to 1.14); heart failure, RR=1.03 (95% CI: 0.67 to 1.59); peripheral vascular disease, RR=0.90 (95% CI: 0.46 to 1.78); leg amputations, RR=1.04 (95% CI: 0.44 to 2.44); and microvascular complications, RR=0.83 (95% CI: 0.59 to 1.17). For all-cause mortality and cardiovascular mortality, there was significant heterogeneity when including the UK Prospective Diabetes Study subgroups (I(2)=41% and 59%). There was significant interaction with sulphonylurea as a concomitant treatment for myocardial infarction (p=0.10 and 0.02, respectively).
Although metformin is considered the gold standard, its benefit/risk ratio remains uncertain. We cannot exclude a 25% reduction or a 31% increase in all-cause mortality. We cannot exclude a 33% reduction or a 64% increase in cardiovascular mortality. Further studies are needed to clarify this situation.
Poor adherence to asthma controller medications results in poor treatment outcomes. Objectives: To compare controller medication adherence and clinical outcomes in 612 adults with poorly controlled asthma randomized to one of two different treatment decision-making models or to usual care.
In shared decision making (SDM), nonphysician clinicians and patients negotiated a treatment regimen that accommodated patient goals and preferences. In clinician decision making, treatment was prescribed without specifically eliciting patient goals/preferences. The otherwise identical intervention protocols both provided asthma education and involved two in-person and three brief phone encounters.
Refill adherence was measured using continuous medication acquisition (CMA) indices-the total days' supply acquired per year divided by 365 days. Cumulative controller medication dose was measured in beclomethasone canister equivalents. In follow-up Year 1, compared with usual care, SDM resulted in: significantly better controller adherence (CMA, 0.67 vs. 0.46; P < 0.0001) and long-acting beta-agonist adherence (CMA, 0.51 vs. 0.40; P = 0.0225); higher cumulative controller medication dose (canister equivalent, 10.9 vs. 5.2; P < 0.0001); significantly better clinical outcomes (asthma-related quality of life, health care use, rescue medication use, asthma control, and lung function). In Year 2, compared with usual care, SDM resulted in significantly lower rescue medication use, the sole clinical outcome available for that year. Compared with clinician decision making, SDM resulted in: significantly better controller adherence (CMA, 0.67 vs. 0.59; P = 0.03) and long-acting beta-agonist adherence (CMA, 0.51 vs. 0.41; P = 0.0143); higher cumulative controller dose (CMA, 10.9 vs. 9.1; P = 0.005); and quantitatively, but not significantly, better outcomes on all clinical measures.
Negotiating patients' treatment decisions significantly improves adherence to asthma pharmacotherapy and clinical outcomes. Clinical trials registered with www.clinicaltrials.gov (NCT00217945 and NCT00149526).
We recently proposed that the biological markers improved by carbohydrate restriction were precisely those that define the metabolic syndrome (MetS), and that the common thread was regulation of insulin as a control element. We specifically tested the idea with a 12-week study comparing two hypocaloric diets (approximately 1,500 kcal): a carbohydrate-restricted diet (CRD) (%carbohydrate:fat:protein = 12:59:28) and a low-fat diet (LFD) (56:24:20) in 40 subjects with atherogenic dyslipidemia. Both interventions led to improvements in several metabolic markers, but subjects following the CRD had consistently reduced glucose (-12%) and insulin (-50%) concentrations, insulin sensitivity (-55%), weight loss (-10%), decreased adiposity (-14%), and more favorable triacylglycerol (TAG) (-51%), HDL-C (13%) and total cholesterol/HDL-C ratio (-14%) responses. In addition to these markers for MetS, the CRD subjects showed more favorable responses to alternative indicators of cardiovascular risk: postprandial lipemia (-47%), the Apo B/Apo A-1 ratio (-16%), and LDL particle distribution. Despite a threefold higher intake of dietary saturated fat during the CRD, saturated fatty acids in TAG and cholesteryl ester were significantly decreased, as was palmitoleic acid (16:1n-7), an endogenous marker of lipogenesis, compared to subjects consuming the LFD. Serum retinol binding protein 4 has been linked to insulin-resistant states, and only the CRD decreased this marker (-20%). The findings provide support for unifying the disparate markers of MetS and for the proposed intimate connection with dietary carbohydrate. The results support the use of dietary carbohydrate restriction as an effective approach to improve features of MetS and cardiovascular risk.
Metabolic Syndrome (MetS) represents a constellation of markers that indicates a predisposition to diabetes, cardiovascular disease and other pathologic states. The definition and treatment are a matter of current debate and there is not general agreement on a precise definition or, to some extent, whether the designation provides more information than the individual components. We consider here five indicators that are central to most definitions and we provide evidence from the literature that these are precisely the symptoms that respond to reduction in dietary carbohydrate (CHO). Carbohydrate restriction is one of several strategies for reducing body mass but even in the absence of weight loss or in comparison with low fat alternatives, CHO restriction is effective at ameliorating high fasting glucose and insulin, high plasma triglycerides (TAG), low HDL and high blood pressure. In addition, low fat, high CHO diets have long been known to raise TAG, lower HDL and, in the absence of weight loss, may worsen glycemic control. Thus, whereas there are numerous strategies for weight loss, a patient with high BMI and high TAG is likely to benefit most from a regimen that reduces CHO intake. Reviewing the literature, benefits of CHO restriction are seen in normal or overweight individuals, in normal patients who meet the criteria for MetS or in patients with frank diabetes. Moreover, in low fat studies that ameliorate LDL and total cholesterol, controls may do better on the symptoms of MetS. On this basis, we feel that MetS is a meaningful, useful phenomenon and may, in fact, be operationally defined as the set of markers that responds to CHO restriction. Insofar as this is an accurate characterization it is likely the result of the effect of dietary CHO on insulin metabolism. Glucose is the major insulin secretagogue and insulin resistance has been tied to the hyperinsulinemic state or the effect of such a state on lipid metabolism. The conclusion is probably not surprising but has not been explicitly stated before. The known effects of CHO-induced hypertriglyceridemia, the HDL-lowering effect of low fat, high CHO interventions and the obvious improvement in glucose and insulin from CHO restriction should have made this evident. In addition, recent studies suggest that a subset of MetS, the ratio of TAG/HDL, is a good marker for insulin resistance and risk of CVD, and this indicator is reliably reduced by CHO restriction and exacerbated by high CHO intake. Inability to make this connection in the past has probably been due to the fact that individual responses have been studied in isolation as well as to the emphasis of traditional therapeutic approaches on low fat rather than low CHO.
We emphasize that MetS is not a disease but a collection of markers. Individual physicians must decide whether high LDL, or other risk factors are more important than the features of MetS in any individual case but if MetS is to be considered it should be recognized that reducing CHO will bring improvement. Response of symptoms to CHO restriction might thus provide a new experimental criterion for MetS in the face of on-going controversy about a useful definition. As a guide to future research, the idea that control of insulin metabolism by CHO intake is, to a first approximation, the underlying mechanism in MetS is a testable hypothesis.
The National Cholesterol Education Program’s Adult Treatment Panel III report (ATP III)1 identified the metabolic syndrome as a multiplex risk factor for cardiovascular disease (CVD) that is deserving of more clinical attention. The cardiovascular community has responded with heightened awareness and interest. ATP III criteria for metabolic syndrome differ somewhat from those of other organizations. Consequently, the National Heart, Lung, and Blood Institute, in collaboration with the American Heart Association, convened a conference to examine scientific issues related to definition of the metabolic syndrome. The scientific evidence related to definition was reviewed and considered from several perspectives: (1) major clinical outcomes, (2) metabolic components, (3) pathogenesis, (4) clinical criteria for diagnosis, (5) risk for clinical outcomes, and (6) therapeutic interventions.
ATP III viewed CVD as the primary clinical outcome of metabolic syndrome. Most individuals who develop CVD have multiple risk factors. In 1988, Reaven2 noted that several risk factors (eg, dyslipidemia, hypertension, hyperglycemia) commonly cluster together. This clustering he called Syndrome X , and he recognized it as a multiplex risk factor for CVD. Reaven and subsequently others postulated that insulin resistance underlies Syndrome X (hence the commonly used term insulin resistance syndrome ). Other researchers use the term metabolic syndrome for this clustering of metabolic risk factors. ATP III used this alternative term. It avoids the implication that insulin resistance is the primary or only cause of associated risk factors. Although ATP III identified CVD as the primary clinical outcome of the metabolic syndrome, most people with this syndrome have insulin resistance, which confers increased risk for type 2 diabetes. When diabetes becomes clinically apparent, CVD risk rises sharply. Beyond CVD and type 2 diabetes, individuals with metabolic syndrome seemingly are susceptible to other conditions, notably polycystic ovary syndrome, fatty liver, cholesterol gallstones, asthma, sleep disturbances, and some …
Inappropriate medication use is wide spread especially in older people and is associated with risks including adverse drug reactions, hospitalisation and increased mortality. Optimising appropriate medication use to minimise these harms is an ongoing challenge in health care. The term 'deprescribing' has been utilised to describe the complex process that is required for safe and effective medication cessation. Patients play an important role in their own health, and while they may complain about the number of medications they have to take, they may also be reluctant to actually cease a medication when given the opportunity to do so. A review of previously proposed deprescribing processes and relevant literature was used to develop the patient-centred deprescribing process; a five step cycle that encompasses gaining a comprehensive medication history, identifying potentially inappropriate medications, determining if the potentially inappropriate medication can be ceased, planning the withdrawal regimen (e.g. tapering where necessary) and provision of monitoring, support and documentation. This is the first deprescribing process developed utilising the knowledge of patients' views of medication cessation; it focuses on engaging the patient throughout the process with the aim of improving long-term health outcomes. Despite a comprehensive review of the literature, there is still a lack in the evidence base on which to conduct deprescribing. The next step in broadening the evidence to support deprescribing will be to test the developed process to determine feasibility in the clinical setting.
Several studies investigated the effect of pioglitazone and rosiglitazone on aminotransferases and liver histology in adults with NASH. In an early uncontrolled open-label study117 in 22 subjects with biopsy-proven NASH, rosiglitazone improved aminotransferases and hepatic steatosis, ballooning and inflammation scores, but not fibrosis. But in a subsequent RCT, Ratziu et al.118 observed that rosiglitazone improved aminotransferases and hepatic steatosis, but not necroinflammation or fibrosis and its two-year open-label extension phase also showed similar results.119 Belfort et al.120 conducted a RCT of pioglitazone (45 mg/day) in patients with NASH who had impaired glucose tolerance or T2DM. Although there was a significant weight gain (2.5 ± 0.5 kg) with pioglitazone, it significantly improved aminotransferases, steatosis, ballooning, and inflammation. The NAS improved with pioglitazone in 73% compared to 24% of placebo-treated patients (P
The ability of insulin to stimulate glucose uptake can vary substantially in non-obese individuals with no apparent disease (10). In addition, differences in either degree of obesity or level of habitual physical activity can also modulate in vivo insulin action (18,24). In an apparent attempt to maintain glucose homeostasis, the compensatory response to a decrease in insulin-stimulated glucose up take is an increase in plasma insulin concentration. A defect in the ability of insulin-stimulated glucose uptake has also been demonstrated (21) in patients with either impaired glucose tolerance (IGT) or non-insulin dependent diabetes mellitus (NIDDM). It has been suggested that the degree to which glucose tolerance deteriorates in these individuals is a function of the level of compensatory hyperinsulinemia that they can maintain, and the appearance of severe fasting hyperglycemia marks the failure of the pancreatic beta cell to sustain the necessary increase in insulin secretory response (21).
Metformin, a biguanide antihyperglycemic medication, lowers blood glucose in patients with type 2 diabetes with minimal risk of hypoglycemia. Most common side effects include diarrhea, nausea and vomiting. Extended-release metformin (Glucophage XR)*, a once-daily tablet using the patented GelShield Diffusion System release mechanism, may be better tolerated than immediate-release metformin (Glucophage). This retrospective chart review examined the overall gastrointestinal (GI) tolerability of both formulations.
Patient charts were reviewed and data were collected from October 2001 to May 2002. Adult patients with type 2 diabetes started on extended-release metformin (metformin-XR) or switched from immediate-release metformin to metformin-XR within the previous 2 years were eligible for inclusion in the metformin-XR cohort. Patients started on immediate-release metformin within the previous 2 years were eligible for inclusion in the immediate-release metformin cohort. Previous experience of GI side effects while taking immediate-release metformin did not prevent inclusion in either cohort, though patients with significant underlying GI disease or moderate to severe hepatic or renal impairment were excluded. GI tolerability was assessed during the first year of treatment with immediate-release metformin or metformin-XR. Primary endpoints were overall GI tolerability and frequency of diarrhea during the first year of treatment.
A total of 471 patients' charts were reviewed and data were collected from four diabetes clinics; 310 (metformin-XR) and 158 (immediate-release metformin) eligible patients were included. Patients were, on average, 56 years old, and overweight (mean body mass index 33 kg/m2). The majority of patients were Caucasian (50%), Hispanic (24%) or Black (19%). Mean daily doses were 1258 mg (range 500-2500 mg) for metformin-XR and 1282 mg (range 500-2550 mg) for immediate-release metformin. About 25% of the metformin-XR cohort had been switched from immediate-release metformin due to a history of GI adverse events (AE). Despite this, the frequency of any GI AE was similar between metformin-XR and immediate release metformin (11.94 vs. 11.39%, p = 0.86). The incidence of individual GI AE also did not differ significantly between cohorts. In a cohort of 205 patients started on immediate-release metformin and switched to metformin-XR, the frequency of any GI AE was 26.34% (while taking immediate release metformin; n = 205) vs. 11.71% (after switching to metformin-XR; n = 205) (p = 0.0006) and the frequency of diarrhea was 18.05% (while taking immediate-release metformin) vs. 8.29% (after switching to metformin-XR) (p = 0.0084).
In this retrospective chart review, patients switched from immediate-release metformin to metformin-XR experienced fewer GI side effects on comparable doses of the extended-release metformin.
Shared decision making (SDM) has been recommended as a standard of care, especially when there are treatment alternatives or uncertainty in outcomes. However, we know little about use of SDM in cancer care, and even less is known about SDM in older patients. We describe patient and physician determinants of SDM in older women with breast cancer and evaluate whether SDM is associated with treatment patterns or short-term outcomes of care.
Women age 67 or older treated for early stage breast cancer in 29 sites from five geographic regions comprise the study sample (N = 718). Data were obtained from patients by in-person and telephone interviews. Physician data were collected via survey, and medical records were reviewed to ascertain comorbidity and tumor characteristics. Random effects and logistic regression models were used to assess associations between SDM and other factors.
Women who were age 67 to 74 years (v 75 or older) were accompanied to consultation and who sought information reported the highest SDM, after considering covariates. While SDM was not associated with surgical treatment, greater SDM was associated with higher odds of having adjuvant treatment, controlling for clinical factors. Greater SDM was also associated with improved short-term satisfaction.
SDM plays an important role in the process of care for older women with breast cancer. Physicians treating this growing population have a simple, but powerful tool for improving outcomes within their grasp-spending time to engage and involve older women in their breast cancer care.
The ability for aminotransferase levels to track histological features of non-alcoholic fatty liver disease (NAFLD) with weight loss has not been examined.
We examined the effect of weight loss following laparoscopic adjustable gastric banding surgery on the histological features of NAFLD and plasma aminotransferase concentrations (AST, ALT and GGT) in 60 (12M, 48F) selected severely obese patients. All 120 paired biopsies were de-identified and scored for lobular steatosis, fibrosis, inflammation, Mallory bodies and NASH.
30 patients (50%) had baseline histological features of non-alcoholic steatohepatitis (NASH). Repeat biopsies were taken at 29.5+/-10 months after baseline. Mean weight loss was 31.5+/-18 kg. There were improvements in AST, ALT, GGT, lobular steatosis, inflammation and fibrosis between baseline and follow-up (P<0.001 for all). Only 6 (10%) of repeat biopsies showed NASH. No change in aminotransferase concentrations predicted the change in steatosis, but changes in AST and GGT predicted improved scores for inflammation, fibrosis, Mallory bodies and NASH. The lowering of GGT best predicted the improvements in inflammation, fibrosis and NASH.
With weight loss, falls in GGT and, to a lesser extent, in AST, are predictive of improved lobular inflammation and fibrosis, key prognostic features of NAFLD.
To determine whether serum gamma-glutamyl transferase (GGT) predicts cardiovascular disease (CVD) morbidity and mortality, accounting for temporal changes in known CVD risk factors and C-reactive protein (CRP).
In 3451 Framingham Study participants (mean age 44 years, 52% women) we examined the relations of GGT with CVD risk factors, and prospectively determined the risk of new-onset metabolic syndrome, incident CVD, and death. GGT was positively associated with body mass index, blood pressure, LDL cholesterol, triglycerides, and blood glucose in cross-sectional analysis (P<0.005). On follow-up (mean 19 years), 968 participants developed metabolic syndrome, 535 developed incident CVD, and 362 died. The risk of metabolic syndrome increased with higher GGT (multivariable-adjusted hazard ratio [HR] per SD increment log-GGT, 1.26 [95%CI; 1.18 to 1.35]). Adjusting for established CVD risk factors (as time-dependent covariates updated quadriennially) and baseline CRP, a 1-SD increase in log-GGT conferred a 13% increase in CVD risk (P=0.007) and 26% increased risk of death (P<0.001). Individuals in the highest GGT quartile experienced a 67% increase in CVD incidence (multivariable-adjusted HR 1.67, 95%CI; 1.25 to 2.22).
An increase in serum GGT predicts onset of metabolic syndrome, incident CVD, and death suggesting that GGT is a marker of metabolic and cardiovascular risk.
What role do people want to play in treatment decision-making (DM)?
Examine the role patients indicate they would prefer in making treatment decisions across multiple clinical settings in Ontario, Canada.
Secondary analysis of a series of survey/interview-based studies measuring preferred role, conducted in 12 different populations.
Respondents were outpatients, largely but not entirely attending outpatient clinics in large teaching hospitals in urban settings in the Province of Ontario, Canada. The subgroups and sample sizes were: breast cancer (202), prostate disease (202), fractures (202), continence (46), orthopaedic (111), rheumatology (56), multiple sclerosis (22), HIV/AIDS (431), infertility (454), benign prostatic hyperplasia (678) and cardiac disease (300), plus 50 healthy nursing students (for scale validation).
All studies categorized preferred role using the Problem-Solving Decision-Making (PSDM) scale with one or both of the Current Health condition and Chest Pain vignettes.
Few respondents preferred an autonomous role (1.2% for the current health condition vignette and 0.7% for the chest pain vignette); most preferred shared DM (77.8% current health condition; 65.1% chest pain) or a passive role (20.3% current health condition; 34.1% chest pain). Familiarity with a clinical condition increases desire for a shared (as opposed to passive) role. Preferences for passive vs. shared roles varied across settings; older and less educated individuals were most likely to prefer passive roles.
Despite consumerist rhetoric among some bioethicists, very few respondents wish an autonomous role. Most wish to share DM with their providers.