Stephanie B. Mayer

Conflicting Results Between Randomized Trials and Observational Studies on the Impact of Proton Pump Inhibitors on Cardiovascular Events When Coadministered With Dual Antiplatelet Therapy Systematic Review

Background— Discordant results have been reported on the effects of concomitant use of proton pump inhibitors (PPIs) and dual antiplatelet therapy (DAPT) for cardiovascular outcomes. We conducted a systematic review comparing the effectiveness and safety of concomitant use of PPIs and DAPT in the postdischarge treatment of unstable angina/non–ST-segment–elevation myocardial infarction patients. Methods and Results— We searched for clinical studies in MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews, from 1995 to 2012. Reviewers screened and extracted data, assessed applicability and quality, and graded the strength of evidence. We performed meta-analyses of direct comparisons when outcomes and follow-up periods were comparable. Thirty-five studies were eligible. Five (4 randomized controlled trials and 1 observational) assessed the effect of omeprazole when added to DAPT; the other 30 (observational) assessed the effect of PPIs as a class when compared with no PPIs. Random-effects meta-analyses of the studies assessing PPIs as a class consistently reported higher event rates in patients receiving PPIs for various clinical outcomes at 1 year (composite ischemic end points, all-cause mortality, nonfatal MI, stroke, revascularization, and stent thrombosis). However, the results from randomized controlled trials evaluating omeprazole compared with placebo showed no difference in ischemic outcomes, despite a reduction in upper gastrointestinal bleeding with omeprazole. Conclusions— Large, well-conducted observational studies of PPIs and randomized controlled trials of omeprazole seem to provide conflicting results for the effect of PPIs on cardiovascular outcomes when coadministered with DAPT. Prospective trials that directly compare pharmacodynamic parameters and clinical events among specific PPI agents in patients with unstable angina/non–ST-segment–elevation myocardial infarction treated with DAPT are warranted.

Two diets with different haemoglobin A1c and antiglycaemic medication effects despite similar weight loss in type 2 diabetes.

We analysed participants with type 2 diabetes (n = 46) within a larger weight loss trial (n = 146) who were randomized to 48 weeks of a low‐carbohydrate diet (LCD; n = 22) or a low‐fat diet + orlistat (LFD + O; n = 24). At baseline, mean body mass index (BMI) was 39.5 kg/m2 (s.d. 6.5) and haemoglobin A1c (HbA1c) 7.6% (s.d. 1.3). Although the interventions reduced BMI similarly (LCD −2.4 kg/m2; LFD + O −2.7 kg/m2, p = 0.7), LCD led to a relative improvement in HbA1c: −0.7% in LCD versus +0.2% in LFD + O [difference −0.8%, 95% confidence interval (CI) = −1.6, −0.02; p = 0.045]. LCD also led to a greater reduction in antiglycaemic medications using a novel medication effect score (MES) based on medication potency and total daily dose; 70.6% of LCD versus 30.4% LFD + O decreased their MES by ≥50% (p = 0.01). Lowering dietary carbohydrate intake demonstrated benefits on glycaemic control beyond its weight loss effects, while at the same time lowering antiglycaemic medication requirements.

Effect of Allowing Choice of Diet on Weight Loss: A Randomized Trial

Context Permitting a choice in the diet to follow has been proposed as a means to improve weight-loss efforts. Contribution This randomized trial found that patients who were allowed to choose their diets did not lose more weight than those whose diets were assigned to them. Caution Only 2 diet choices were offered. Implication The ability to choose a diet might not improve weight-loss results. Various dietary approaches have been shown to be effective for weight management, alleviation of risk factors, and disease prevention (19). Regardless of the approach, greater adherence to dietary recommendations has been the best predictor of weight loss (10). Therefore, new strategies that maximize dietary adherence are needed to help patients experience the maximum health benefits. Allowing persons to choose among evidence-based dietary strategies intuitively holds promise for improving dietary adherence because it is patient-centered, offering the opportunity to select a diet on the basis of food preferences or other factors that patients may value. If allowing choice among diets improves weight outcomes, as has been suggested (1113), various dietary approaches could be made available to those seeking weight loss and strategies could be developed to facilitate choice. In this double-randomized preference trial, we evaluated whether participants who were allowed the opportunity to choose between 2 diets would lose more weight than those randomly assigned to a diet. Methods Setting and Participants Details of the study protocol have been reported elsewhere (14). Participants were recruited from clinics of the Durham Veterans Affairs Medical Center (VAMC) in Durham, North Carolina, between May 2011 and June 2012. Participants were eligible if they had a body mass index (BMI) of at least 30 kg/m2, a regular VAMC provider, access to a telephone, and reliable transportation. Participants were ineligible for the following reasons: aged 75 years or older, serum creatinine level greater than 132.6 mol/L (>1.5 mg/dL) (men) or greater than 114.9 mol/L (>1.3 mg/dL) (women), liver disease, type 1 diabetes, hemoglobin A1c level of 12% or greater, daily insulin use, unstable heart disease, organ transplant, blood pressure of 160/100 mmHg or greater, fasting triglyceride level of 6.8 mmol/L (600 mg/dL) or greater, low-density lipoprotein cholesterol level of 4.9 mmol/L (190 mg/dL) or greater, pregnancy, breastfeeding, lack of birth control if premenopausal, dementia, severe psychiatric illness, recent substance abuse, recent weight-loss attempt, or presence of a pacemaker or defibrillator. Outpatients who met entry criteria for age, BMI, and VAMC provider and lived within a 50-mile radius were mailed a letter inviting them to call if they were interested in participating. Patients could also self-refer via advertisements posted in clinics or could be referred by health care personnel. Research assistants assessed eligibility using the electronic medical record; a telephone screen; and an in-person screen, at which written, informed consent was obtained. Potential participants who expressed a strong aversion to one of the diets were informed that they might be randomly assigned to that diet and should enroll only if that would be acceptable. The Institutional Review Board of the Durham VAMC approved the study. Randomization We randomly assigned eligible participants in parallel fashion and a 1:1 ratio to the choice or comparator group by using a computerized random-number generator in blocks of fewer than 10, stratified by sex, BMI (<40 or 40 kg/m2), and diagnosis of type 2 diabetes. Comparator participants underwent a second 1:1 randomization to either the low-carbohydrate diet (LCD) or the low-fat diet (LFD). Only the study statisticians were aware of the randomization sequence. The project coordinator entered final eligibility data into the database, which automatically generated the group assignment for eligible participants. Participants were not made aware of their assignment and were thus not considered randomly assigned until their first group visit. Interventions Choice Group Procedures At the first group visit, choice group participants received summary results from the Geiselman Food Preference Questionnaire (FPQ), which was administered at the screening visit and indicated which of the 2 diet options their preferences aligned with (15). The FPQ uses a Likert scale of 1 (dislike extremely) to 9 (like extremely) to assess preferences for 72 foods that are common sources of macronutrients in the typical U.S. diet. Participants scoring higher in the Low Carbohydrate/High Protein summary category of the FPQ were advised that their food preferences aligned best with the LCD, whereas those scoring higher in the Low Fat/High Simple Sugar or Low Fat/High Complex Carbohydrate categories were advised that their preferences aligned best with the LFD. Participants then received verbal and printed information about the 2 diets, including foods emphasized and deemphasized, sample menus, and evidence for safety and efficacy. Participants were asked not to discuss their decision with other study participants but were allowed to consult with nonparticipants. Participants were advised that they could use all of this information to inform their choice of diet. The following week, the study dietitian called participants to elicit their diet choice, with diet counseling starting at the subsequent group visit. At this stage of enrollment, participants in each of 4 cohorts (approximately 50 per cohort) were placed into 4 small groups of approximately 12 participants each (choice-LCD, choice-LFD, comparator-LCD, and comparator-LFD). At week 12, choice participants had the option of switching to the other diet, in which case they received personal counseling for the new diet and subsequently joined the corresponding choice diet group. Comparator Group Procedures At the first group visit, comparator group participants learned of their diet assignment and received an overview of the study design and procedures but were advised not to begin the diet until the subsequent study visit to parallel the timeline of the choice group. Comparator participants then received counseling specific to their randomly assigned diet for the duration of the study. Procedures Common to All Participants Group sessions occurred every 2 weeks for 24 weeks, then every 4 weeks for 24 weeks, with a telephone call from the dietitian between these monthly sessions. In both groups, sessions consisted of measurements followed by group counseling by a single study dietitian. Counseling consisted of dietary and physical activity topics as well as behavioral elements (such as mindful eating and planning for high-risk situations). A pocket guide to counting calories, fat, and carbohydrates was provided (16). Participants were advised to strive for 30 minutes of moderate-intensity aerobic physical activity 5 days per week (17). A study physician was available as needed for antihypertensive or antiglycemic medication adjustments that followed an algorithm (Appendix Figures 1, 2, 3, and 4). Appendix Figure 1. Initial diabetes medication adjustment. HbA1c = hemoglobin A1c; Met = metformin; Secret = secretagogues; TZD = thiazolidinediones. Appendix Figure 2. Medication adjustment for follow-up hypoglycemia in patients taking medication in addition to metformin. GLP-1 = glucagon-like peptide-1. Appendix Figure 3. Medication adjustment for follow-up hypoglycemia in patients taking metformin only. am = morning; bid = twice daily; pm = evening; qd = every day. Appendix Figure 4. Medication adjustment for hypertensive patients taking medication. The telephone counseling focused on individual goal setting and problem solving and incorporated principles of motivational interviewing (18). Using a script, the dietitian helped the patient identify and rank possible goals and then develop and refine action plans (19). The dietitian recorded the goals and action plans electronically so that progress could be assessed during subsequent calls. Dietary Interventions Participants received a book and printed handouts specific to the diet they were following (20, 21). For the LCD, carbohydrate intake was initially restricted to approximately 20 g/d, but calories were not restricted (7, 22). Participants were instructed on how to increase carbohydrate intake gradually as they neared their weight-loss goal or if cravings threatened adherence. For the LFD, intake of total fat was restricted to less than 30% of the daily energy intake, intake of saturated fat was restricted to less than 10% of the daily energy intake, intake of cholesterol was restricted to less than 300 mg/d (21, 23), and energy intake was restricted by subtracting 500 kcal from the daily maintenance energy requirement (24). Outcome Measures Body weight, the primary outcome, was measured at each of the 19 visits at the same time of day on a standardized digital scale with participants in light clothing and shoes removed. Secondary outcomes were measured every 12 weeks for a total of 5 measurements. Waist circumference was measured with a nonelastic tape measure placed on the skin horizontally at the iliac crest (23). Dietary adherence was assessed using the Block Brief 2000 Food Frequency Questionnaire (FFQ), which assesses more than 70 food items (25). A summary measure of dietary adherence was calculated because the LCD and LFD have different dietary goals. The measure was calculated beginning at 12 weeks because dietary adherence did not apply at baseline. The calculation was the percentage of deviation from the goal macronutrient intake, with lower values considered to be greater adherence. For the LFD, the goal was no more than 30% of daily calories from fat. For the LCD, the goal was no more than 10% of daily calories from carbohydrates, based on our previous study showing that this was the mean percentage intake at 2 weeks (22). Weig

Considering patient diet preference to optimize weight loss: design considerations of a randomized trial investigating the impact of choice.

A variety of diet approaches achieve moderate weight loss in many individuals. Yet, most diet interventions fail to achieve meaningful weight loss in more than a few individuals, likely due to inadequate adherence to the diet. It is widely conjectured that targeting the diet to an individuals food preferences will enhance adherence, thereby improving weight loss. This article describes the design considerations of a study protocol aimed at testing this hypothesis. The study is a 2-arm randomized trial recruiting 216 medical outpatients with BMI ≥30 kg/m(2) followed for 48 weeks. Participants in the experimental arm (Choice) select from two of the most widely studied diets for weight loss, a low-carbohydrate, calorie-unrestricted diet (LCD) or a low-fat, reduced-calorie diet (LFD). The participants choice is informed by results from a validated food preference questionnaire and a discussion of diet options with trained personnel. Choice participants are given the option to switch to the other diet after three months, if desired. Participants in the Control arm are randomly assigned to follow one of the two diets for the duration of follow-up. The primary outcome is weight assessed every 2-4 weeks for 48 weeks. Secondary outcomes include adherence to diet by food frequency questionnaire and obesity-specific health-related quality of life. If assisting patients to choose their diet enhances adherence and increases weight loss, the results will support the provision of diet options to patients who desire weight loss, and bring us one step closer to remediating the obesity epidemic faced by our healthcare systems.